Omega-3 fatty acids and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with endometriosis: an experimental study.

OBJECTIVE: To assess whether follicular fluid (FF) from infertile women with endometriosis in advanced stages [moderate/severe (EIII/IV) without or with endometrioma (Endometrioma)] induce more oocyte damages than in early stages (minimal/mild: EI/II); and whether supplementation with L-carnitine (LC) and omega 3 (n3) can prevent these oocyte damages. METHODS: Experimental study using bovine oocytes (obtained of ovaries from slaughterhouse), and human FF (samples were obtained during oocyte recovery for ICSI). Bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no FF(No-FF), with 1% FF from infertile women without endometriosis (FFC), with EI/II, EIII/IV and Endometrioma, and with (or not) LC+n3 addition. After IVM, oocytes were fluorescently labelled and visualized by confocal microscopy to analyze chromosomes and spindle. RESULTS: FF from endometriosis decreased rate of normal MII (spindle assembly and chromosome alignment) compared to No-FF (87.2%) and FFC (87.2%). FFEIII/IV (80.7%) and FFEndometrioma (69.3%) decreased total MII rate compared to No-FF (91.9%) and FFC (89.2%), and FFEndometrioma had lower total MII rate compared to other groups. LC+n3 increased MII rate in the FFEIII/IV (80.7% vs. 90.8%) and the Endometrioma (69.3% vs. 86.4%), and it prevented damages in spindle and chromosomes in MII oocytes in the FFEI/II group (62.2% vs. 84.5%) and the FFEIII/IV group (70.2% vs. 84.1%). CONCLUSIONS: FF of endometriosis damaged the meiotic spindle of bovine MII oocytes. EIII/IV led to impaired nuclear maturation; FF from women with endometrioma had further negative impact in oocyte maturation. LC+n3 completely prevented the effects of FF from women with endometriosis on oocyte.

Phosphatidylcholine and L-acetyl-carnitine-based freezing medium can replace egg yolk and preserves human sperm function.

BACKGROUND: Conventional cryopreservation methods induce chemical and mechanical damage to the sperm membranes. The cryoprotectant potential of phospholipids of vegetal origin as soybean lecithin has been investigated as a substitute for egg yolk in diluents used for the cryopreservation of human spermatozoa. Therefore, the objective of this study was comparing the efficacy of a synthetic cryoprotectant supplemented with L-α-phosphatidylcholine (PC) and L-acetyl-carnitine (ANTIOX-PC) and the standard egg-based TEST-yolk buffer (TYB) in preserving sperm motility and chromatin quality in cryopreserved semen samples. METHODS: Prospective experimental study in which semen samples from 63 men with normal sperm motility and 58 men with low sperm motility were included and analyzed both before and after cryopreservation using ANTIOX-PC or TYB freezing media. Sperm quality was evaluated by routine semen analysis and DNA fragmentation index using the Terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: Differences in the post-thaw progressive motility and DNA fragmentation index were not detected between TYB and ANTIOX-PC cryoprotectants in both normal and low sperm motility groups (P>0.05). However, ANTIOX-PC medium retained higher non-progressive motility and lower percentage of immotile sperm when compared to TYB medium, resulting in a greater total motile sperm count (P<0.05), regardless baseline values of motility characteristic of the normospermic or asthenozoospermic samples. CONCLUSIONS: ANTIOX-PC medium was effective to protect human sperm during a freeze-thaw cycle compared to the TYB medium. A clinically relevant advantage in better preserving kinetic parameters as higher total motility and lower immotile post-thawed sperm from ANTIOX-PC, in normal and low motility semen samples, demonstrated the positive impact of phospholipid and antioxidant treatment on sperm cryotolerance with high potential for egg yolk lipids replacement and biosafety.

O uso de tamoxifeno e inibidores da aromatase na terapia endócrina pra o câncer de mama / The use of tamoxifen and aromatae inhibitors for breast cancer endocrine therapy

A terapia endócrina para tumores de mama com receptores hormonais positivos é amplamente usada tanto de forma paliativa no câncer de mama metastático, quanto na adjuvância, para tumores iniciais. O tamoxifeno (TMX) tem sido usado como droga de escolha com este propósito há cerca de 30 anos com boa eficácia e perfil razoavelmente seguro. O desenvolvimento dos inibidores de aromatase (IAs) de terceira geração promoveu estudos comparativos que têm demonstrado superioridade dos IAs em relação ao TMX na adjuvância, favorecendo seu uso tanto em substituição, quanto de forma seqüencial. Em geral, os IAs são tão bem tolerados quanto o TMX, preocupando ainda questões como aumento de risco cardiovascular, de osteoporose e alterações no perfil lipídico. Nos últimos dois anos, importantes instituições como a American Society of Clinical Oncology (ASCO), o National Comprehensive Cancer Network (NCCN) e o Consenso Internacional de St. Gallen (Consenso de St. Gallen) passaram, em vista das evidências emergentes, a indicar o uso dos IAs em detrimento do TMX para as mulheres após a menopausa com tumores sensíveis ao tratamento endócrino.

Endocrine therapy for breast cancer with positive receptors has been widely applied either for advanced metastatic cancer as for initial tumors. For more than 30 years tamoxifen (TMX) has been the first choice for this purpose with an acceptable safety profile. The emerging third generation aromatase inhibitors (IA) promoted comparative trials which have proved the IA to be superior to TMX in the adjuvant setting - what supported its use both in substitution and in a sequential manner. Broadly, the IA are as well tolerated as TMX, still concerning issues as cardiovascular risk and osteoporosis increase and lipid profile changes. During the last couple of years, institutions as the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN) and the International St. Gallen Consensus have changed their recommendations advising the use of IA instead of TMX as a first choice treatment for post-menopause women with sensitive breast cancer.

Ação de drogas que reduzem a resistência insulínica na síndrome nos ovários policísticos / Insulin resistance and Pcos: insulin-lowering agents

A síndrome dos ovários policísticos (SOP)afeta entre 10 a 20 porcento da população feminina. Várias são as etiologias propostas para explicar a síndrome, que se caracteriza por irregularidade menstrual; hiperandrogenismo e ovários policísticos à ultra-sonografia. A resistência à insulina parece ter papel determinante sobre a fisiopatologia da SOP, devido a alterações moleculares nos receptores para insulina, que levam a não utilização da mesma, com consequente aumento compensatório da excreção pelas células pancreáticas. A resistência insulínica causa aumento dos níveis de androgênios circulantes e de hormônio luteinizante, reduz as proteínas carreadoras de esteróides sexuais e altera o perfil lipídico. A utilização de hipoglicemiantes orais leva à reversão do processo fisiopatológico com melhora clínica e laboratorial dos pacientes. São revistas, neste estudo, as ações descritas para as diversas drogas já testadas nesta síndrome

Etiopatogenia da endometriose: o que há de novo? / Etiopathogenesis of endometriosis: What is new?

Os Mecanismos envolvidos na etiopatogenia da endometriose continuam parcialmente esclarecidos e aberrações moleculares emergem como possíveis alvos de defeitos. A teoria mais aceita é a do fluxo retrógrado, postulada por Sampson em 1929. Entretanto, foi comprovado que praticamente 90 por cento das mulheres com trompas pérvias apresentam fluxo retrógrado e somente 10 por cento delas apresentarão endometriose. Isto nos leva a pensar que outros fatores associados ao fluxo retrógrado permitiriam a implantação deste tecido na cavidade abdominal. Acredita-se em comprometimento poligênico que resulta em alterações moleculares de citocinas, de enzimas relacionadas à esteroidogênese, como a aromatase, e de moléculas envolvidas com o estresse oxidativo celular, além daquelas responsáveis pela adesão, invasão, neovascularização, crescimento e manutenção das células endometriais refluídas pelas trompas durante a menstruação. Estas alterações tornam tanto o endométrio tópico quanto o microambiente peritoneal das mulheres com endometriose favorável ao desenvolvimento dos implantes endometrióticos e desfavorával ao processo reprodutivo