Murine endometrial-derived mesenchymal stem cells suppress experimental autoimmune encephalomyelitis depending on indoleamine-2,3-dioxygenase expression.

Cellular therapy with mesenchymal stem cells (MSCs) is a huge challenge for scientists, as little translational relevance has been achieved. However, many studies using MSCs have proved their suppressive and regenerative capacity. Thus, there is still a need for a better understanding of MSCs biology and the establishment of newer protocols, or to test unexplored tissue sources. Here, we demonstrate that murine endometrial-derived MSCs (meMSCs) suppress Experimental Autoimmune Encephalomyelitis (EAE). MSC-treated animals had milder disease, with a significant reduction in Th1 and Th17 lymphocytes in the lymph nodes and in the central nervous system (CNS). This was associated with increased Il27 and Cyp1a1 expression, and presence of IL-10-secreting T CD4+ cells. At EAE peak, animals had reduced CNS infiltrating cells, histopathology and demyelination. qPCR analysis evidenced the down-regulation of several pro-inflammatory genes and up-regulation of indoleamine-2,3-dioxygenase (IDO). Consistently, co-culturing of WT and IDO-/- meMSCs with T CD4+ cells evidenced the necessity of IDO on the suppression of encephalitogenic lymphocytes, and IDO-/- meMSCs were not able to suppress EAE. In addition, WT meMSCs stimulated with IL-17A and IFN-γ increased IDO expression and secretion of kynurenines in vitro, indicating a negative feedback loop. Pathogenic cytokines were increased when CD4+ T cells from AhR-/- mice were co-cultured with WT meMSC. In summary, our research evidences the suppressive activity of the unexplored meMSCs population, and shows the mechanism depends on IDO-kynurenines-Aryl hydrocarbon receptor (AhR) axis. To our knowledge this is the first report evidencing that the therapeutic potential of meMSCs relying on IDO expression.

Is time since vasectomy more important as prognostic factor for pregnancy and live birth than female and laboratory variables when treating vasectomised man using ICSI?

Fatherhood after vasectomy can be done by vasectomy reversal or intracytoplasmic sperm injection (ICSI). Time since vasectomy is the best predictive factor for patency and live birth after a vasectomy reversal but has uncertain importance after ICSI with sperm retrieval. The present study examines the influence of male, female and laboratory variables on pregnancy and live birth. The study is based on 450 ICSI cycles from 332 patients performed on three infertility centres between 1994 and 2012. Interval time since vasectomy was divided in four groups GI-less than 3 years (n = 02); GII-3 to 8 years (n = 74); GIII-9 to 14 years (n = 161) and GIV-15 or more years (n = 213). The variables were tested for pregnancy rate and live birth for first and repeated cycles. Pregnancy and live birth rate were not statistically different among the study interval time groups for first or repeated cycles. Female and laboratory variables were statistically different for couples with pregnancy and live birth for the first cycles. The study suggests that variables coming from female and laboratory were more important than time since vasectomy when treating man with vasectomy using ICSI with sperm retrieval.

Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System.

Mesenchymal stem cells comprise a natural reservoir of undifferentiated cells within adult tissues. Given their self-renewal, multipotency, regenerative potential and immunomodulatory properties, MSCs have been reported as a promising cell therapy for the treatment of different diseases, including neurodegenerative and autoimmune diseases. In this study, we investigated the immunomodulatory properties of human tubal mesenchymal stem cells (htMSCs) using the EAE model. htMSCs were able to suppress dendritic cells activation downregulating antigen presentation-related molecules, such as MHCII, CD80 and CD86, while impairing IFN-γ and IL-17 and increasing IL-10 and IL-4 secretion. It further correlated with milder disease scores when compared to the control group due to fewer leukocytes infiltrating the CNS, specially Th1 and Th17 lymphocytes, associated with increased IL-10 secreting Tr1 cells. Conversely, microglia were less activated and infiltrating mononuclear cells secreted higher levels of IL-4 and IL-10 and expressed reduced chemokine receptors as CCR4, CCR6 and CCR8. qPCR of the spinal cords revealed upregulation of indoleamine-2,3-dioxygenase (IDO) and brain derived neurotrophic factor (BDNF). Taken together, here evidenced the potential of htMSCs as an alternative for the treatment of inflammatory, autoimmune or neurodegenerative diseases.

Light-emitting diode stimulates radiodermatitis recovery.

PURPOSE: To evaluate the effect of light-emitting diode (LED) in an experimental model of radiodermatitis. METHODS: Ten male Wistar rats weighing 200-250 g were analyzed. Radiation was delivered in a single dose (20 Gy with Strontium-90 dermatological plaques), two areas per animal. After 15 days, they were divided into two groups: control group (n = 5) and LED group (n = 5), which was treated during 21 days later (LED 660 nm, 10 min in alternate days). The endpoints were radiodermatitis scale, histological analysis HE, Picrius Sirius and the gene expression of interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9). RESULTS: The LED group showed a higher number of dermal appendages (p = 0.04) and angiogenesis(p = 0.007), a tendency towards higher IL-10 (p = 0.06) and an increase in MMP-9 (p = 0.004) when compared to the control group. CONCLUSIONS: This study suggested that the use of LED for radiodermatitis increased skin regeneration.

Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET).

PURPOSE: To assess the potential effects of short-term exposure to particulate air pollution during follicular phase on clinical, laboratory, and pregnancy outcomes of women undergoing IVF/ET. METHODS: Retrospective cohort study of 400 first IVF/ET cycles of women exposed to ambient particulate matter during follicular phase. Particulate matter (PM) was categorized into quartiles (Q(1): < or =30.48 microg/m(3), Q(2): 30.49-42.00 microg/m(3), Q(3): 42.01-56.72 microg/m(3), and Q(4): >56.72 microg/m(3)). RESULTS: Clinical, laboratory, or treatment variables were not affected by follicular phase PM exposure periods. Women exposed to Q(4) period during the follicular phase of conception cycles had a higher risk of miscarriage (odds ratio, 5.05; 95% confidence interval: 1.04-25.51) when compared to women exposed to Q(1-3) periods. CONCLUSION: Our results show an association between brief exposure to high levels of ambient PM during the preconceptional period and early pregnancy loss, although no effect of this exposure on clinical, laboratory, and treatment outcomes was observed.

Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures.

BACKGROUND: The possibility of using stem cells for regenerative medicine has opened a new field of investigation. The search for sources to obtain multipotent stem cells from discarded tissues or through non-invasive procedures is of great interest. It has been shown that mesenchymal stem cells (MSCs) obtained from umbilical cords, dental pulp and adipose tissue, which are all biological discards, are able to differentiate into muscle, fat, bone and cartilage cell lineages. The aim of this study was to isolate, expand, characterize and assess the differentiation potential of MSCs from human fallopian tubes (hFTs). METHODS: Lineages of hFTs were expanded, had their karyotype analyzed, were characterized by flow cytometry and underwent in vitro adipogenic, chondrogenic, osteogenic, and myogenic differentiation. RESULTS: Here we show for the first time that hFTs, which are discarded after some gynecological procedures, are a rich additional source of MSCs, which we designated as human tube MSCs (htMSCs). CONCLUSION: Human tube MSCs can be easily isolated, expanded in vitro, present a mesenchymal profile and are able to differentiate into muscle, fat, cartilage and bone in vitro.

Bloodstream Infections in Early Postsurgery Liver Transplant: An Analysis of 401 Patients Over 10 Years.

Bloodstream infections are a major factor contributing to morbidity and mortality following liver transplantation. The increasing occurrence of multidrug-resistant bloodstream infections represents a challenge for the prevention and treatment of those infections. The aim of this study was to evaluate the occurrence and microbiological profile of bloodstream infections during the early postoperative period (from day 0 to day 60) in patients undergoing liver transplantation from January 2005 to June 2016 at the State University of Campinas General Hospital. A total of 401 patients who underwent liver transplantation during this period were included in the study. The most common cause of liver disease was hepatitis C virus cirrhosis (34.01%), followed by alcoholic disease (16.24%). A total of 103 patients had 139 microbiologically proven bloodstream infections. Gram-negative bacteria were isolated in 63.31% of the cases, gram-positive bacteria in 28.78%, and fungi in 7.91%. Fifty-six infections (43.75%) were multidrug-resistant bacteria, and 72 (56.25%) were not. There was no linear trend concerning the occurrence of multidrug-resistant organisms throughout the study period. Patients with multidrug-resistant bloodstream infections had a significantly lower survival rate than those with no bloodstream infections and those with non-multidrug-resistant bloodstream infections. In conclusion, the occurrence of bloodstream infections during the early postoperative period was still high compared with other profile patients, as well as the rates of multidrug-resistant organisms. Even though the occurrence of multidrug resistance has been stable for the past decade, the lower survival rates associated with that condition and the challenge related to its treatment are of major concern.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1ß, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

Human fallopian tube mesenchymal stromal cells enhance bone regeneration in a xenotransplanted model.

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30-50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)-a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% ß-tricalciumphosphate-only, and the right side (RS) with the CellCeram and htMSCs (10(6) cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction.

Biological effects and dose-response assessment of diesel exhaust particles on in vitro early embryo development in mice.

An increased risk of early pregnancy loss in women briefly exposed to high levels of ambient particulate matter during the preconceptional period was recently observed. The effects of this exposure on early embryo development are unknown. This study was designed to assess the dose-response and biological effects of diesel exhaust particles (DEP) on in vitro embryo development using the in vitro fertilization (IVF) mouse model. Zygotes obtained from superovulated mice after IVF were randomly cultured in different DEP concentrations (0, 0.2, 2, and 20 microg/cm(2)) for 5 days and observed for their capacity to attach and develop on a fibronectin matrix until day 8. Main outcome measures included blastocyst rates 96 and 120 h after insemination, hatching discriminatory score, total cell count, proportion of cell allocation to inner cell mass (ICM) and trophectoderm (TE), ICM morphology, attachment rate and outgrowth area, apoptosis and necrosis rates, and Oct-4 and Cdx-2 expression. Multivariate analysis showed a negative dose-dependent effect on early embryo development and hatching process, blastocyst cell allocation, and ICM morphology. Although blastocyst attachment and outgrowth were not affected by DEP, a significant impairment of ICM integrity was observed in day 8 blastocysts. Cell death through apoptosis was significantly higher after DEP exposure. Oct-4 expression and the Oct-4/Cdx-2 ratio were significantly decreased in day 5 blastocysts irrespective of DEP concentration. Results suggest that DEP appear to play an important role in disrupting cell lineage segregation and ICM morphological integrity even at lower concentrations, compromising future growth and viability of the blastocyst.

Effects of exposure to high levels of particulate air pollution during the follicular phase of the conception cycle on pregnancy outcome in couples undergoing in vitro fertilization and embryo transfer.

The objective of this retrospective cohort study was to assess the potential effects of preconceptional short-term exposure to particulate air pollution in a real-world situation on pregnancy outcome in infertile women evaluating the possible role of IVF/embryo transfer treatment on this outcome using women who had conceived naturally for the first time during the same time frame as a matched control group. The study provides evidence for an association between brief exposure to high levels of ambient particulate matter (aerodynamic diameter

In vitro fertilization, embryo development, and cell lineage segregation after pre- and/or postnatal exposure of female mice to ambient fine particulate matter.

OBJECTIVE: To evaluate effects of pre- and/or postnatal exposure to ambient fine particulate matter on fertilization, embryo development, and cell lineage segregation in preimplantation blastocysts using the IVF mouse model. DESIGN: Animal model. SETTING: Academic institution. ANIMAL(S): Six-week-old, superovulated mice. INTERVENTION(S): Pre- and postnatal exposure to filtered air (FA-FA), filtered-ambient air (FA-AA), or ambient air (AA-AA) in exposure chambers 24 hours a day for 9 weeks. MAIN OUTCOME MEASURE(S): Gestation length, litter size, sex ratio, ovarian response to superovulation, fertilization rate, embryo development, blastocyst and hatching rates, total cell count, and proportion of cell allocation to inner-cell mass (ICM) and trophectoderm (TE). RESULT(S): Gestation length, litter size and birth weight, live-birth index, and sex ratio were similar among exposure groups. Ovarian response was not affected by the exposure protocol. A multivariate effect for pre- and/or postnatal exposure to ambient fine particulate matter on IVF, embryo development, and blastocyst differential staining was found. Cell counts in ICM and ICM/TE ratios in blastocysts produced in the FA-FA protocol were significantly higher than in blastocysts produced in the FA-AA and AA-AA protocols. No difference in total cell count was observed among groups. CONCLUSION(S): Our study suggests that exposure to ambient fine particulate matter may negatively affect female reproductive health by disrupting the lineage specification at the blastocyst stage without interfering in early development of the mouse embryo.

Comparison of the efficacy of two commercially available media for culturing one-cell embryos in the in vitro fertilization mouse model.

OBJECTIVE: To examine the effects of two commercial media on the development of mouse ova fertilized in vitro to the blastocyst stage. DESIGN: Animal model. SETTING: Academic institution. ANIMAL(S): Eight-week old, superovulated mice. INTERVENTION(S): One-cell embryos cultured in vitro up to the blastocyst stage in potassium-enriched simplex optimized medium (KSOM) or G1/G2 medium. MAIN OUTCOME MEASURE(S): Blastocyst and hatching rates, total cell number count, and proportion of allocation of cells to the inner cell mass (ICM) and trophectoderm (TE). RESULT(S): The percentage of zygotes that developed to the blastocyst stage 96 and 120 hours after insemination was statistically significantly higher in the KSOM group. The percentage of blastocysts that partially or completely hatched by day 5 of culture was 84% and 71% for the KSOM and G1/G2 groups, respectively, showing a statistically significant difference between the groups. The mean number of ICM cells was 11.7 +/- 4.0 and 9.2 +/- 5.2 for the zygotes cultured in KSOM and G1/G2 media, respectively, revealing a statistically significantly higher cell number in the ICM of blastocysts derived from culture in KSOM medium. The ICM/TE ratio in the blastocysts cultured in KSOM or G1/G2 media was similar in both groups. CONCLUSION(S): Commercially available KSOM medium is superior to sequential G1/G2 media for culturing one-cell embryos up to the blastocyst stage in the mouse IVF model.

Prevalência de oclusopatias e comparação entre a Classificação de Angle e o Índice de Estética Dentária em escolares do interior do estado de São Paulo - Brasil / Malocclusion prevalence and comparison between the Angle classification and the Dental Aesthetic Index in scholars in the interior of São Paulo state - Brazil

INTRODUÇÃO: as oclusopatias estão entre os principais problemas de saúde bucal em todo o mundo, juntamente com a cárie dentária e a doença periodontal, e vários índices têm sido utilizados para registrá-las. OBJETIVOS: verificar a prevalência de oclusopatias utilizando a Classificação de Angle e o Índice de Estética Dentária (DAI), sua severidade e a necessidade de tratamento ortodôntico registradas pelo DAI, e comparar os resultados de ambos os índices, visando correlacionar o padrão dos dados coletados e a viabilidade de utilizá-los de forma conjunta. MÉTODOS: a amostra consistiu de 734 escolares com idade de 12 anos, de ambos os sexos, da rede pública do município de Lins/SP. Foram realizados exames nos pátios das escolas com utilização de sondas IPC a olho nu. RESULTADOS: pela Classificação de Angle, encontrou-se 33,24 por cento das crianças com oclusão normal e 66,76 por cento com má oclusão. Pelo DAI, observou-se que 65,26 por cento das crianças apresentavam-se sem anormalidades ou com más oclusões leves. A má oclusão definida esteve presente em 12,81 por cento, a má oclusão severa foi observada em 10,90 por cento e a muito severa ou incapacitante em 11,03 por cento. A maioria das crianças (70,57 por cento) apresentou relação molar normal, e o overjet maxilar anterior foi a alteração mais frequentemente observada. No cruzamento dos índices houve semelhanças e divergências. CONCLUSÃO: o DAI não foi sensível a alguns problemas de oclusão detectados pela Classificação de Angle, e a recíproca foi verdadeira, demonstrando que ambos os índices possuem pontos distintos na detecção das oclusopatias, podendo ser utilizados de forma reciprocamente complementar.

INTRODUCTION: The malocclusions are among the main buccal health problems all over the world, together with dental cavity and periodontal disease. Several indexes are being used for malocclusion registration. The present study verified the prevalence of this condition, using the Angle classification and the Dental Aesthetic Index (DAI), the severity and the necessity of orthodontic treatment registered with the DAI and the results of both indexes were compared, seeking to correlate collected data pattern and the viability of using them together. METHODS: The sample consisted of 734 schoolchildren with 12 years of age, both male and female from the public municipal schools in Lins-SP, Brazil. The exams were performed at the school's playgrounds with the use of IPC probes with a naked eye. RESULTS: For the Angle classification, it was found that 33.24 percent of the children presented normal occlusion and 66.76 percent presented malocclusions. It was observed, with the DAI, that 65.26 percent of the children had no abnormalities or had slight malocclusions. The defined malocclusion was present in 12.81 percent, severe malocclusion was observed in 10.90 percent and very severe or disabling malocclusion in 11.03 percent. Most of the children (70.57 percent) presented normal molar relationship and the anterior maxillary overjet was the most frequently observed alteration. When the indexes were compared there were similarities and divergences. CONCLUSION: DAI was not sensitive for some occlusion problems detected by the Angle classification, and vice-versa, demonstrating that both indexes have different points in malocclusions detection, so they could be used mutually in a complementary way.

Efeitos da exposição pré-concepcional de curta duração ao material particulado ambiental sobre o mecanismo reprodutivo feminino / Effects of short-term preconceptional exposure to ambient particulate matter on female reproductive function

Um Projeto Temático de Pesquisa foi desenvolvido no Laboratório de Poluição Ambiental do Departamento de Patologia da Faculdade de Medicina da Universidade de São Paulo com o objetivo de avaliar os efeitos da exposição aguda/crônica ao ar ambiente de um grande centro urbano sobre a saúde. Dentro deste projeto, uma linha de pesquisa foi dedicada ao estudo dos efeitos dessa exposição sobre a saúde reprodutiva feminina. Evidências de estudos epidemiológicos e experimentais implicam os fatores ambientais na infertilidade humana e resultado obstétrico adverso. Contudo, poucos estudos foram conduzidos até o presente para avaliar um possível efeito da exposição à poluição ambiental particulada sobre a saúde reprodutiva feminina. Portanto, o objetivo dos projetos da minha linha de pesquisa é fornecer dados que possam demonstrar os possíveis efeitos da exposição pré-concepcional de curta duração às partículas de exaustão do diesel (PED) e à poluição ambiental particulada sobre a função ovariana, o desenvolvimento embrionário inicial e resultado gestacional utilizando um modelo experimental e um epidemiológico. O objetivo do primeiro projeto desta tese foi avaliar os efeitos de dois meios de cultura comerciais no desenvolvimento de oócitos de camundongo fertilizados in vitro até o estágio de blastocisto. Zigotos obtidos de fêmeas de camundongo de 8 semanas de idade submetidas à indução da ovulação foram cultivados in vitro até o estágio de blastocisto em meio simples otimizado enriquecido com potássio (KSOM) ou meio G1/G2. A porcentagem de zigotos que se desenvolveu até o estágio de blastocisto 96 e 120 horas após a inseminação e que sofreu eclosão parcial ou completa no quinto dia de cultivo foi significativamente maior no grupo KSOM. O número médio de células da massa celular interna (MCI) foi 11,7 ± 4,0 e 9,2 ± 5,2 para os zigotos cultivados nos grupos KSOM e G1/G2, respectivamente, mostrando um número significativamente maior de células MCI em blastocistos...

A thematic research project to evaluate the health effects of acute/chronic exposure to ambient air in a large urban center was developed at the Air Pollution Laboratory in the Department of Pathology at the University of São Paulo School of Medicine. Within this project a specific research line was committed to the study of the effects of this exposure on female reproductive health. Evidence from epidemiological and experimental studies implied environmental factors as possible contributors to human infertility and poor obstetric outcome. However, very few studies evaluating a possible effect of exposure to particulate air pollution on female reproductive health have been conducted so far. Thus, the aim of the projects in my research line was to provide data that could show the possible effects of short-term preconceptional exposure to diesel exhaust particles and particulate air pollution on ovarian function, early embryo development and pregnancy outcome using experimental and epidemiological models. The objective of the first project was to examine the effects of two commercial media on the development of mouse ova fertilized in vitro to the blastocyst stage. One-cell embryos obtained from eight-week old superovulated mice were cultured in vitro up to the blastocyst stage in potassium-enriched simplex optimized medium (KSOM) or G1/G2 media. The percentage of zygotes that developed to the blastocyst stage 96 and 120 hours after insemination and that partially or completely hatched by day five of culture was significantly higher in the KSOM group. The mean number of inner cell mass (ICM) cells was 11.7 ± 4.0 and 9.2 ± 5.2 for zygotes cultured in KSOM and G1/G2 groups respectively, revealing a significantly higher cell number in the ICM of blastocysts derived from culture in KSOM medium. I concluded that commercially available KSOM medium is superior to sequential G1/G2 media for culturing one-cell embryos up to the blastocyst stage in...

Influência de dois cateteres diferentes de transferência de embriöes sobre as taxas de gestaçäo em um programa de fertilizaçäo in vitro humana / The influence of two different transfer catheters on the pregnancy rate in a human in vitro fertilization program

OBJETIVO: Comparar as taxas de gravidez de 248 ciclos consecutivos de fertilizaçäo in vitro (FIVETE) utilizando-se dois cateteres diferentes para a transferência intra-uterina dos embriöes. INTERVENÇÃO: Estudo prospectivo, randomizado. MATERIAL E MÉTODOS: Foi utilizado o protocolo longo de estimulaçäo ovariana em todos os ciclos. A transferência de "prova", com o objetivo de mapear o canal cervical, foi realizada em todos os ciclos imediatamente antes da aspiraçäo folicular. A avaliaçäo morfológica e graduaçäo embrionária foram realizadas pelo mesmo embriologista e todas as transferências intra-uterinas transcervicais de embriöes foram realizadas pelo mesmo ginecologista 42 a 48 horas após a inseminaçäo dos oócitos. O cateter T.D.T. (Prodimed, França) foi usado em 120 tentativas (grupo A) e 128 transferências embrionárias foram realizadas com o cateter Tefcat (Cook, USA) (grupo B). Os dois cateteres foram carregados de acordo com a mesma seqüência. RESULTADOS: As pacientes dos 2 grupos näo mostraram diferença significativa com relaçäo à idade, duraçäo da infertilidade, índice de massa corpórea ou da duraçäo da estimulaçäo. ICSI foi realizado em todos os casos de fator masculino de infertilidade. Níveis séricos médios de E2, espessura e padräo endometrial e, número de folículos identificados no dia da administraçäo do hCG foram similares nos 2 grupos. O número médio de oócitos M2 inseminados e fertilizados e o número de embriöes clivados foram 8,8 ñ 3,7, 6,5 ñ 3,3 para o grupo A e 9,4 ñ 5,4, 6,8 ñ 4,6 e 5,8 ñ 4,3 para o grupo B, respectivamente, näo revelando diferença entre os grupos. A qualidade embrionária (classificaçäo de Veeck) e a taxa de desenvolvimento embrionário (número de blastômeros/embriäo antes da transferência) foram 1,89 ñ 0,8 e 3,5 ñ 1,4 (grupo A) e 1,88ñ0,8 e 3,26 ñ 1,0 (grupo B), respectivamente, näo mostrando diferença entre os grupos. O número de embriöes transferidos foi similar nos 2 grupos (4,0ñ1,6 e 4,1ñ0,4; grupos A e B, respectivamente). A opiniäo do ginecologista sobre a transferência foi anotada como fácil ou difícil em 104 e 16 ciclos e em 104 e 24 ciclos para os grupos A e B, respectivamente, näo demonstrando diferença entre os grupos. Traçäo cervical com pinça de Pozzi foi realizada em 52 e 56 ciclos (grupos A e B, respectivamente) (p=0.941). A contaminaçäo do cateter com sangue e muco cervical foi mais freqüente (p=0.02) no grupo A (44/120) quando comparada ao grupo B (24/128)...

Padröes de desenvolvimento folicular em ciclos espontâneos e induzidos de pacientes inférteis portadoras de endometriose pélvica leve / Follicle growth patterns in spontaneous and induced cycles in infertili women with mild endometriosis

OBJETIVOS: avaliar os padroes de desenvolvimento folicular em ciclos espontâneos (CE) e os efeitos da hiperestimulaçao ovariana controlada com citrato de clomifeno (CC) e/ou gonadotrofina de mulher menopausada (HMG) e gonadotrofina coriônica humana (HCG) sobre a foliculogênese e taxas de gestaçao de pacientes inférteis portadoras de endometriose leve. MÉTODO: A avaliaçao sonográfica transvaginal seriada da dinâmica folicular foi realizada em 88 ciclos (CE, 21; CC/HMG/hCG, 29; HMG/HCG, 38) de 19 pacientes inférteis portadoras de endometriose pélvica (grupo de estudo) em comparaçao com 98 ciclos (CE, 27; CC/hMG/ hCG, 42; hMG/hCG, 29) de 21 casais portadores de infertilidade masculina (grupo controle). RESULTADOS: Foliculogênese normal foi observada em 50 (56.8 por cento) ciclos do grupo de estudo e em 88 (89.8 por cento) ciclos do grupo controle (p

Potencial ovulatório e reprodutivo de um coorte de folículos ovarianos no dia da administraçåo da gonadotrofina coriônica humana (HCG) em ciclos induzidos com citrato de clomifeno (CC) e/ou gonadotrofina de mulher menopausada / Ovulatory and reproductive potential of a cohort of follicles at the time of human chorionic gonadotropin (hCG) administration in clomiphene citrate and/or human menopausal gonadotropin-stimulated cycles

O presente estudo tem como objetivos comparar os parâmetros ultra-sonográficos do desenvolvimento folicular e endometrial, avaliar o potencial ovulatório de cada folículo ovariano de acordo com seu respectivo diâmetro médio (DFM) em resposta à gonadotrofina coriônica humana (HCG) e analisar a possível influência de cada um desses parâmetros nas taxas de gestaçåo de ciclos induzidos com o citrato de clomifeno (CC) e/ou gonadotrofina de mulher menopausada (HMG). Cento e três pacientes normoestrogênicas inférteis foram submetidas a 125 ciclos de hiperestimulaçåo ovariana controlada e foram divididas em dois grupos de acordo com o protocolo de estimulaçåo utilizado: grupo A (n=48) - HMG/HCG e grupo B (n=56) - CC/HMG/HCG. Verificou-se uma reduçåo de 36,4 por cento do núemro de ampolas de HMG utilizadas no grupo B (p<0,001), quando comparado ao grupo A. A distribuiçåo dos diagnósticos de infertilidade nåo revelou diferença entre os grupos. A Ultra-sonografia transvaginal seriada foi realizada diariamente, com o objetivo de avaliar o crescimento folicular, a espessura endometrial e as taxas de ovulaçåo por DFM no dia da administraçåo do HCG. As taxas de gestaçåo foram comparadas entre os grupos. As porcentagens de folículos medindo 12mm, 13-14mm, 15-16mm, 17-18mm, 19-20mm e > 20mm no dia da administraçåo do HCG, que subseqüentemente ovularam, foram 0 por cento e 0 por cento; 19,4 por cento e 23,2 por cento; 38,5 por cento e 66,1 por cento; 72,2 por cento e 91,7 por cento; 88,6 por cento e 97,6 por cento; 100 por cento e 92,3 por cento para os grupos A e B, respectivamente, nåo se observando diferença entre os dois grupos. As taxas de ovulaçåo foram significativamente menores (p<0,002, p<0,05; grupos A e B, respectivamente) para os folículos com DFM 16mm, quando comparados estes àqueles com DFM 17mm. O número total de folículos, ovulaçöes e espessura endometrial no dia da confirmaçåo da ovulaçåo nåo apresentou diferença quando ciclos com ou sem gestaçåo foram comparados. Considerando-se os ciclos com gestaçåo dos dois grupos, a distribuiçåo do DFM no dia da administraçåo do HCG, dos folículos que ovularam, foi significativamente diferente (p<0,001). A incidência de folículos com DFM 17mm no dia da administraçåo do HCG foi significativamente maior (p=0,01) nos ciclos de gestaçåo do grupo A quando comparados a estes ciclos do grupo B. Gestaçöes clínicas foram observadas em 17 (29,3 por cento) e 11 (16,4 por cento) ciclos dos grupos A e B, respectivamente, nåo se verificando diferença estatística entre os dois grupos (p=0,08). Os autores concluem que: (1) DFM 17mm no dia da administraçåo do HCG correlaciona-se com altas taxas de ovulaçåo em protocolos de hiperestimulaçåo ovariana controlada que utilizam CC e/ou HMG; (2) uma vez que nåo há diferença significativa nas taxas de gestaçåo entre os dois grupos e que o número de ampolas de HMG utilizadas em protocolo CC/HMG é menor, esta associaçåo represaenta uma opçåo atraente como primeira escolha em ciclos de hiperestimulaçåo ovariana controlada, independenetmente do diagnóstico da infertilidade; (3) o atraso na administraçåo do HCG pode ser necessário naqueles pacientes que recebem CC/HMG com a finalidade de aumentar o número de folículos com DFM 17mm e, talvez, as taxas de gestaçåo deste grupo

O emprego do citrato de clomifeno e gonadotrofina de mulher menopausada como alternativa de hiperestimulaçäo ovariana em pacientes com resposta idiopática inadequada na fertilizaçäo in vitro / Clomiphene citrate and gonadotropins of woman in menopause as an alternative approach to ovarian hyperstimulation in idiopatic poor response for in vitro fertilization

OBJETIVO: Avaliar os efeitos do esquema de estimulaçäo ovariana com citrato de clomifeno (CC)/gonadotrofina de mulher menopausada (hMG) nos resultados da fertilizaçäo in vitro e transferência de embriöes (FIVETE) em um grupo de pacientes que apresentaram resposta ovariana inadequada em ciclos prévios de FIVETE estimulados com um análogo do GnRH e gonadotrofinas (protocolo longo). MÉTODO: Os resultados de FIVETE em ciclos estimulados com CC/hMG e com o protocolo longo de uma mesma paciente foram comparados. Oito pacientes (grupo I) que apresentaram uma resposta ovariana idiopática inadequada (idade: < 38 anos, FSH<15 mU/mL, E2<60pg/mL, ciclos menstruais regulares e ausência de cirurgia ovariana) ao protocolo longo em 11 ciclos de FIVETE (grupo Ia), foram estimuladas com CC/hMG em 20 ciclos (grupo Ib). Administrou-se CC 100 mg/dia por 5 dias a partir do 3§ dia do ciclo e o hMG 150 UI/dia foi iniciado no 5§ dia, sendo a dose modificada de acordo com a resposta da paciente. Dezenove ciclos de 15 pacientes com resposta ovariana adequada ao protocolo longo, durante o mesmo intervalo de tempo, foram incluídas neste estudo como grupo controle (grupo II). Casais com fator masculino de infertilidade foram excluídos. RESULTADOS: As pacientes avaliadas näo apresentaram diferença em termos de idade, duraçäo da infertilidade e do índice de massa corpórea. Embora a duraçäo do estímulo ovariano tenha sido similar nos 3 grupos: 10,1 + 0,76, 10,9 + 0,34 e 10,3 + 0,21 dias para os grupos Ia, Ib e II, respectivamente, o número médio de ampolas de hMG utilizado no grupo Ib (13,6 + 1,36) foi significativamente menor (p<0.001) quando comparado aos grupos Ia e II (49,9 + 3,20, 43,7 + 2,73; respectivamente). A taxa de cancelamento foi de 36,4 por cento, 25,0 por cento e 0 por cento (grupos Ia, Ib e II; respectivamente), näo revelando diferença entre os grupos Ia e Ib. Os números médios de oócitos MII inseminados e fertilizados foram de 4,9 + 0,8 e 1,3 + 0,4 no grupo Ia e de 4,4 + 0,3 e 2,1 + 0,2 no grupo Ib, näo mostrando diferença entre os grupos. Contudo, os números médios de oócitos MII inseminados e fertilizados no grupo II, 11,4 + 2,0 (p<0.01) e 7,9 + 2,0 (p=0.01), respectivamente, foram significativamente maiores quando comparados aqueles do grupos Ia e Ib...