Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas.

Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation, malignancy, and therapeutic resistance, but is still few elucidated in canine mammary tumor subtypes. Here, we first validated, using CMT samples, a previously published canine one-class logistic regression machine learning algorithm (OCLR) to predict stemness (mRNAsi) in canine cancer cells. Then, using the canine mRNAsi, we observed that simple carcinomas exhibit higher stemness than complex carcinomas and other histological subtypes. Also, we confirmed that stemness is higher and associated with basal-like CMTs and with NMF2 metagene signature, a tumor-specific DNA-repair metagene signature. Using correlation analysis, we selected the top 50 genes correlated with higher stemness, and the top 50 genes correlated with lower stemness and further performed a gene set enrichment analysis to observe the biological processes enriched for these genes. Finally, we suggested two promise stemness-associated targets in CMTs, POLA2 and APEX1, especially in simple carcinomas. Thus, our work elucidates stemness as a potential mechanism behind the aggressiveness and development of canine mammary tumors, especially in simple carcinomas, describing evidence of a promising strategy to target this disease.

Acompanhamento dermatológico de enfermagem na estratégia saúde da família: um relato de experiência / Dermatological nursing care in the family health strategy: an experience report / Cuidados de enfermería dermatológica en la estrategia de salud familiar: informe de una experiencia

O desenvolvimento de lesões por pressão vem sendo um tema bastante discutido dentro e fora do âmbito hospitalar, sendo considerado um indicador de qualidade da assistência hospitalar, quando o aparecimento ocorre mediante uma internação. Cabe ao enfermeiro o acompanhamento dermatológico, avaliação e prescrição de coberturas e correlatos, consoante o estágio da lesão por pressão. Por esta razão, este estudo teve como objetivo descrever a experiência de graduandos de enfermagem durante acompanhamento dermatológico de uma pessoa idosa. Trata-se de um estudo descritivo do tipo relato de experiência realizado entre os meses de fevereiro e maio de 2021. Através da experiência relatada neste estudo, foi possível compreender a complexidade e relevância do cuidado humanizado, e os desafios enfrentados pelo enfermeiro da Estratégia Saúde da Família nos cuidados à pessoa idosa com lesão por pressão. Do ponto de vista acadêmico, essa experiência proporcionou aos alunos confrontar os conhecimentos teóricos acerca do assunto, além de incorporar a importância do olhar holístico para o usuário.

The development of pressure injuries has been a much discussed topic inside and outside the hospital environment, being considered an indicator of the quality of hospital care when the appearance occurs during hospitalization. The trained nurse is responsible for dermatological follow-up, evaluation and prescription of dressings and related items, depending on the stage of the pressure injury. For this reason, this study aimed to describe the experience of nursing students during the dermatological follow-up of an elderly person. This is a descriptive study of the experience report type carried out between the months of February and May 2021. Through the experience reported in this study, it was possible to understand the complexity and relevance of humanized care, and the challenges faced by nurses in the Health Strategy of the Family in the care of the elderly with pressure injuries. From an academic point of view, this experience allowed students to confront theoretical knowledge about the subject, in addition to incorporating the importance of a holistic view for the user.

El desarrollo de las lesiones por presión ha sido un tema muy discutido dentro y fuera del ámbito hospitalario, siendo considerado un indicador de la calidad de la atención hospitalaria cuando su aparición ocurre durante la hospitalización. La enfermera capacitada es responsable del seguimiento dermatológico, evaluación y prescripción de apósitos y artículos relacionados, según la etapa de la lesión por presión. Por eso, este estudio tuvo como objetivo describir la experiencia de estudiantes de enfermería durante el seguimiento dermatológico de una persona mayor. Se trata de un estudio descriptivo del tipo relato de experiencia realizado entre los meses de febrero y mayo de 2021. A través de la experiencia relatada en este estudio fue posible comprender la complejidad y relevancia del cuidado humanizado, y los desafíos enfrentados por los enfermeros en el Estrategia Salud de la Familia en el cuidado del anciano con lesiones por presión. Desde el punto de vista académico, esta experiencia permitió a los estudiantes confrontar conocimientos teóricos sobre el tema, además de incorporar la importancia de una mirada holística para el usuario.

A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates.

Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells.

Expression of LIN28A/B and Let-7 miRNAs in canine mammary carcinomas / Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos

LIN28 is a RNA-binding protein including two highly conserved homologous, LIN28A and LIN28B. Proto-oncogenes such as LIN28A and LIN28B are generally targeted by the let-7 miRNAs in different types of human cancers. Here, we determined the expression of LIN28A in canine mammary tumor samples and the LIN28/let-7 pathway in canine mammary cell lines. In those cell lines, we identified a functional LIN28/let-7 pathway which exhibited high expression of let-7 members and low expression of its targets, including LIN28A and LIN28B. However, the mammary carcinoma tissue samples showed a frequent expression of LIN28A being expressed mainly in the epithelial cells. No association was observed between LIN28A expression and histopathological classification and grade, TNM and survival time. Our results suggested a possible role of the LIN28A protein in the development of canine mammary carcinomas due to the high frequency observed in the tumor samples (28 of 32). The in vitro experiments suggested that the LIN28/let-7 pathway is active in the tumor cells evaluated. However, more studies are necessary to elucidate the exact role of LIN28/let-7 pathway in canine mammary carcinomas.

LIN28 é uma proteína de ligação ao RNA, com duas formas homólogas altamente conservadas, LIN28A e LIN28B. Os proto-oncogenes LIN28A e LIN28B são regulados pela família de miRNAs let-7 em diferentes tipos de cânceres em humanos. No presente trabalho, o objetivo foi determinar a expressão de LIN28A em amostras de tumor mamário de cadelas e a via LIN28/let-7 em linhagens celulares mamárias caninas. Nestas linhagens, através das técnicas de qPCR e RNAseq, foi identificado que a via LIN28/let-7 apresenta-se funcional, com alta expressão dos membros da família let-7 e baixa expressão de seus alvos, entre eles LIN28A e LIN28B. No entanto, as amostras de tecidos de carcinomas mamários caninos demonstraram expressão frequente de LIN28A, sendo observada principalmente em células epiteliais. Não foram observadas associações entre expressão de LIN28A com classificação e gradação histopatológicas, TNM e tempo de sobrevida. Nossos resultados sugerem uma possível relação da proteína LIN28A no desenvolvimento de carcinomas mamários caninos devido à alta frequência observada nas amostras tumorais (28 de 32). Os experimentos in vitro sugerem que a via LIN28/let-7 é ativa nas linhagens celulares caninas avaliadas. Entretanto, estudos funcionais ainda são necessários para elucidar a função exata da via LIN28/let-7 nos carcinomas mamários caninos.

Intercellular interactions between mast cells and stromal fibroblasts obtained from canine cutaneous mast cell tumours.

Mast cell tumours (MCTs) are the most frequent malignant skin neoplasm in dogs. Due to the difficulty in purifying large numbers of canine neoplastic mast cells, relatively little is known about their properties. A reproducible in vitro model is needed to increase the understanding about the phenotype and functional properties of neoplastic mast cells. In the present study, we describe the establishment of primary cocultures of neoplastic mast cells from canine cutaneous MCTs and cancer-associated fibroblasts. We confirmed the inability of canine neoplastic mast cells to remain viable for long periods in vitro without the addition of growth factors or in vivo passages in mice. Using a transwell system, we observed that mast cell viability was significantly higher when there is cell-to-cell contact in comparison to non-physical contact conditions and that mast cell viability was significantly higher in high-grade than in low-grade derived primary cultures. Moreover, the use of conditioned medium from co-cultured cells led to a significantly higher tumoral mast cell viability when in monoculture. Signalling mechanisms involved in these interactions might be attractive therapeutic targets to block canine MCT progression and deserve more in-depth investigations.

Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines.

Canine mammary carcinoma (CMC) is one of the major health threats in dogs. The oncolytic virotherapy is a promising strategy to treat canine as well as human cancer patients with non-pathogenic replicating viruses. Here, we evaluated the antitumor activity of one lentogenic, non-lytic Newcastle disease virus (NDV) LaSota strain expressing GFP (NDV-GFP) on five different CMCs and one non-tumorigenic cell line, regarding cell viability, cell death, selectivity index, morphology, global and target gene expression analysis. As evidenced by the selectivity index, all CMC cell lines were more susceptible to NDV-GFP in comparison with the non-tumorigenic cells (~3.1× to ~78.7×). In addition, the oncolytic effect of NDV-GFP was more evident in more malignant CMC cells. Also, we observed an inverse association of the IFN pathway expression and the susceptibility to NDV. The downregulated genes in NDV-GFP-sensitive cells were functionally enriched for antiviral mechanisms by interferon and immune system pathways, demonstrating that these mechanisms are the most prominent for oncolysis by NDV. To our knowledge, this is the first description of oncolysis by an NDV strain in canine mammary cancer cells. We also demonstrated specific molecular pathways related to NDV susceptibility in these cancer cells, opening the possibility to use NDV as a therapeutic-targeted option for more malignant CMCs. Therefore, these results urge for more studies using oncolytic NDVs, especially considering genetic editing to improve efficacy in dogs.

Epigenetic Mechanisms in Canine Cancer.

A plethora of data has highlighted the role of epigenetics in the development of cancer. Initiation and progression of different cancer types are associated with a variety of changes of epigenetic mechanisms, including aberrant DNA methylation, histone modifications, and miRNA expression. At the same time, advances in the available epigenetic tools allow to investigate and reverse these epigenetic changes and form the basis for the development of anticancer drugs in human oncology. Although human and canine cancer shares several common features, only recently that studies emerged investigating the epigenetic landscape in canine cancer and applying epigenetic modulators to canine cancer. This review focuses on the existing studies involving epigenetic changes in different types of canine cancer and the use of small-molecule inhibitors in canine cancer cells.

An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells.

Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs.

ZEB1 and ZEB2 transcription factors are potential therapeutic targets of canine mammary cancer cells.

Mammary tumours are the most frequent in female dogs as in women and half are malignant. Tumorigenicity and invasiveness are important acquired characteristics for the development and progression of cancers and could be regulated by transcription factors associated with epithelial-mesenchymal transition (EMT) as ZEB1, ZEB2, SNAI1, SLUG and STAT3. Thus, here, we evaluate the expression of EMT-associated transcription factors in canine mammary cancer (CMC) cell lines characterized for invasiveness and tumorigenicity to determine if these could be considered good targets for future development of therapies. Five CMC cell lines were characterized regarding their morphology, doubling time and expression of intermediate and actin filaments. In addition, gene expression of SLUG, STAT3, ZEB1, ZEB2 and CDH1, tumorigenicity and invasiveness were assessed. Two of these cells presented an epithelial-like morphology (E20 and E37) and three a mesenchymal-like morphology (M5, M25 and CF41.Mg). M25 and CF41.Mg presented higher invasiveness. Furthermore, only mesenchymal-like cells formed tumorspheres and CF41.Mg made more and larger tumorspheres. The mesenchymal-like cells are more malignant than the epithelial-like cells being the CF41.Mg the most malignant. This cell presented higher ZEB1 and ZEB2 and lower CDH1 gene expression. Finally, our results revealed that there is a positive correlation between ZEBs and the tumorsphere number and size. In conclusion, these findings support ZEB1 and ZEB2 as potential therapeutic targets for CMC cells, demonstrating a great potential of canine models for comparative and translational studies.

First trimester ß-hCG and estradiol levels in singleton and twin pregnancies after assisted reproduction.

Objective To compare levels of ß-hCG and estradiol collected during the first trimester in singleton and twin pregnancies following assisted reproduction technologies (ART). Methods We prospectively evaluated 50 singleton and 47 dichorionic twin pregnancies that eventually ended in live births. Patients were recruited from a single ART center with standard treatment protocols followed by fresh embryo transfers. Hormone measurements were performed within a narrow gestational age range and analyzed in a single laboratory thus minimizing inter- and intra-assay variability. We measured serum ß-hCG at 13 days after embryo transfer as well as samples of ß-hCG and estradiol at 8-9 weeks+6 days. Results No significant differences existed between singletons and twins in respect to demographic and cycle characteristics. ß-hCG and estradiol were all significantly higher in twins (P<0.05). Conclusion The data confirms the higher levels of ß-hCG and estradiol in twins, pointing to the potential role of these placental hormones in early support of a twin pregnancy.

Can early ß-human chorionic gonadotropin predict birth of singletons and twins after in vitro fertilization?

OBJECTIVE: To assess the predictive value for clinical pregnancy outcome of ß-hCG level at 13 d after embryo transfer. METHODS: Retrospective study of IVF clinical pregnancies diagnosed at 6 weeks. We calculated the value of ß-hCG level at 13 d after embryo transfer to predict live births. RESULTS: We analyzed 177 IVF cycles between 2009 and 2014 (50 singleton births, 50 twin births, 27 sets with a vanishing twin, 43 first trimester singleton pregnancy loss and seven first trimester total twin pregnancy loss). Singleton pregnancies with a ß-hCG concentration <85 mIU/mL had an 89% risk of having a first trimester loss whereas a concentration >386 mU/mL had a 91% chance of a live birth. Twin pregnancies with a concentration <207 mIU/mL had only a 33% chance of delivering twins and a 55% risk of having a vanishing twin; whereas a level >768 mIU/mL was associated with a 81% chance of live twin birth and a low risk (19%) of having a vanishing twin. Age, type and duration of infertility, body mass index (BMI) and number of fertilized oocytes did not affect these calculations. CONCLUSIONS: ß-hCG level at 13 d after embryo transfer might predict outcomes in clinical singleton and twin pregnancies following IVF.

First transplantation of cryopreserved ovarian tissue in Portugal, stored for 10 years: an unexpected indication.

Ovarian tissue cryopreservation represents a valid strategy to preserve ovarian function in patients with a high risk of premature ovarian failure. We present a case of ovarian tissue cryopreservation carried out in an 18-year-old woman after a laparotomy for left adnexal mass with left adnexectomy. Congenital absence of the right ovary was observed during surgery. To preserve fertility, rescue cryopreservation of ovarian tissue was carried out under extreme conditions (without adopting the standard published protocol, not yet available at our centre). Ten years later, transplantation of cryopreserved ovarian tissue was carried out and, shortly after it, restoration of ovarian function was confirmed.

Ventilação mecânica em pediatria: conceitos básicos / Mechanical ventilation in pediatrics: basic concepts

O emprego da ventilação mecânica em Pediatria implica riscos próprios e sua aplicação deve ser cercada de cuidados específicos. Dentro da sala cirúrgica, a anestesia pode produzir diferentes graus de depressão respiratória, sendo necessário o uso de vários modos ventilatórios. A partir do melhor entendimento da fisiologia respiratória e da ampliação do conhecimento acerca do tema, inovações tecnológicas permitiram sensível melhoria na assistência ventilatória prestada aos pacientes pediátricos. O objetivo do presente artigo é revisar conceitos a respeito da fisiologia respiratória da criança, dos sistemas de ventilação em anestesia pediá- trica e dos modos ventilatórios mais utilizados nesse grupo de pacientes - os quais possibilitam reduzir os índices de complicações relacionadas à ventilação mecânica.

The use of pediatric mechanical ventilation involves inherent risks, and its application should be surrounded by specific care. In the operating room, anesthesia can produce different degrees of respiratory depression and the use of various ventilation modes is required. From a better understanding of respiratory physiology and the expansion of the knowledge about this subject, technological innovations have enabled a significant improvement in ventilatory assistance to pediatric patients. The purpose of this article is to review concepts on respiratory physiology of the child, the ventilation systems in pediatric anesthesia and ventilation modes often used in this group of patients - all these enable us to reduce the rate of complications related to mechanical ventilation.

Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.

BACKGROUND: Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed) to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32-4.84; P≤0.001). In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13-16.70; P≤0.05). CONCLUSIONS/SIGNIFICANCE: Estrogen metabolites occur widely in diverse metabolic pathways. In view of the statistically significant association between catechol-estrogens/ DNA adducts and self-reported infertility, we propose that an estrogen-DNA adduct mediated pathway in S. haematobium-induced ovarian hormonal deregulation could be involved. In addition, the catechol-estrogens/ DNA adducts described here represent potential biomarkers for schistosomiasis haematobia.

Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis.

OBJECTIVE: To compare serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) throughout the menstrual cycle in women with and without endometriosis and to quantify the association between these serum markers. METHODS: Twenty five endometriosis patients (ASRM stage III-IV) and 13 controls were followed through one menstrual cycle. VEGF, TNF-alpha and CRP concentrations were measured with enzyme-linked immunosorbent assay in each of the four cycle phases (early and late proliferative and early and late secretory). Non-parametric methods and Pearson's correlation coefficients were used for statistical analysis. RESULTS: Increased serum levels of VEGF in secretory phases and of TNF-alpha in all cycle phases were observed. A positive correlation between CRP and VEGF was found in endometriosis patients but not in controls. CONCLUSIONS: Our results suggest that excessive systemic angiogenic activity is a feature of patients with endometriosis.

The modified Misgav-Ladach versus the Pfannenstiel-Kerr technique for cesarean section: a randomized trial.

BACKGROUND: Modifications to the classic cesarean section technique described by Pfannenstiel and Kerr have been proposed in the last few years. The objective of this trial was to compare intraoperative and short-term postoperative outcomes between the Pfannenstiel-Kerr and the modified Misgav-Ladach (MML) techniques for cesarean section. METHODS: This prospective randomized trial involved 162 patients undergoing transverse lower uterine segment cesarean section. Patients were allocated to one of the two arms: 88 to the MML technique and 74 to the Pfannenstiel-Kerr technique. Main outcome measures were defined as the duration of surgery, analgesic requirements, and bowel restitution by the second postoperative day. Additional outcomes evaluated were febrile morbidity, postoperative antibiotic use, postpartum endometritis, and wound complications. Student's t, Mann-Whitney, and Chi-square tests were used for statistical analysis of the results, and a p < 0.05 was considered as the probability level reflecting significant differences. RESULTS: No differences between groups were noted in the incidence of analgesic requirements, bowel restitution by the second postoperative day, febrile morbidity, antibiotic requirements, endometritis, or wound complications. The MML technique took on average 12 min less to complete (p = 0.001). CONCLUSION: The MML technique is faster to perform and similar in terms of febrile morbidity, time to bowel restitution, or need for postoperative medications. It is likely to be more cost-effective.

Subendometrial and intraendometrial blood flow during the menstrual cycle in patients with endometriosis.

OBJECTIVE: To use power Doppler ultrasound to assess the effect of endometriosis on intraendometrial and subendometrial blood flow during the menstrual cycle. DESIGN: An observational prospective study. SETTING: Academic teaching hospital. PATIENT(S): Thirty patients with histologically confirmed ovarian endometrioma and 15 control women. INTERVENTION(S): Power Doppler ultrasound examination during the menstrual cycle. MAIN OUTCOME MEASURE(S): Intraendometrial and subendometrial color signals assessed by power Doppler ultrasound. RESULT(S): A statistically significant higher proportion of endometrioma patients presented simultaneous intraendometrial and subendometrial color signals in the late secretory cycle phase compared with controls (40.0% vs. 6.7%). CONCLUSION(S): The higher endometrial perfusion in patients with ovarian endometrioma that is observed in the late secretory phase of the cycle, close to menstrual shedding, favors the hypothesis that women with endometriosis might have higher endometrial vascular activity, thus facilitating the implantation process of endometrial cells outside the uterus.

A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy.

OBJECTIVE: To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS). STUDY DESIGN: Phase III, randomized, single center study of 131 patients undergoing COS and IVF with or without ICSI, in a University affiliated Hospital. Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm. The Student's t-test, the Mann-Whitney test and the chi-square test were applied as required, using SPSS for Windows with a two-sided 5% significance level. RESULTS: The mean (+/-S.D.) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group (P=0.02). The mean (+/-S.D.) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group (P<0.0001). No significant differences were noted in other outcome measures: amount of rFSH required, estradiol level on hCG day, number of follicles>or=15 mm and endometrial thickness on oocyte retrieval day, number of oocytes retrieved, fertilization rate and number of OHS cases. Clinical pregnancy rates per-attempt and per-transfer were 15.1% and 17.0% in the antagonist group and 16.9% and 20.0% in the agonist group (P=0.79 and 0.71, respectively). CONCLUSIONS: GnRH antagonists are an effective, safe and well tolerated alternative to agonists for COS.

[Apoptosis and human reproduction]. / Apoptose e reprodução humana.

Apoptosis is a common form of physiological cell death that is essential to maintain homeostasis in human tissues and when deregulated, explains the physiopathological events in most diseases. This is true both in the ovary and uterus, two essential organs for human reproduction. The correct understanding of the role that this phenomenon carry out to regulate ovarian and uterine cellular populations and consequently to regulate reproductive physiology, might allow in the future the development of new strategies to treat infertility. This paper is a review of the current understandings about apoptosis and its involvement in human reproductive physiology.