A review of antifertility folkloric plants tested in laboratory animals

The use of natural active principals is widespread among a great proportion of the rural population, or by people who do not have easy access to medical assistance. These active principles are used as food or medicines, and even for purposes of contraception. It becomes necessary to establish a relationship between the folklore habits and current information on the nature of anti-fertility substances, and knowledge of their mechanisms. Anti-fertility agents may exert their actions in a number of areas, (hypothalamus, anterior pituitary, oviduct, uterus, and vagina), inhibiting synthesis and/or liberation of hormones (follicle-stimulating, luteinizing, and steroid hormones), ovulation, ovum transportation, and implantation process. Therefore, a review of literature was carried out, including of several plants used by women as abortifacient and anti-fertility agents to compare their effects with those obtained among laboratory animals.

Increased implantation and pregnancy rates obtained by placing the tip of the transfer catheter in the central area of the endometrial cavity

The influence of endometrial cavity length (ECL) on implantation and pregnancy rates after 400 embryo transfers was studied prospectively in a population with the indication of IVF/intracytoplasmic sperm injection (ICSI). The tip of the transfer catheter was placed above or below the half point of the ECL in a randomized manner. Two analyses were performed: (i) absolute position (AP); embryo transfers were divided into three groups according to the distance between the end of the fundal endometrial surface and the catheter tip (DTC - distance tip catheter): AP 1 (n = 212), 10-15 mm; AP 2 (n = 158), 16-20 mm; and AP 3 (n = 30), ≥21 mm. (ii) relative position (RP) - embryo transfers were divided into four groups according to their RP [RP = (DTC/ECL) × 100]: RP 1 (n = 23), ≤40%; RP 2 (n = 177), 41-50%; RP 3 (n = 117), 51-60%; and RP 4 (n = 83), ≥61%. Analysis based on relative distance revealed significantly higher implantation and pregnancy rates (P < 0.05) in more central areas of the ECL. However, analysis based on absolute position did not reveal any difference. In conclusion, the present results demonstrated that implantation and pregnancy rates are influenced by the site of embryo transfer, with better results being obtained when the catheter tip is positioned close to the middle area of the endometrial cavity. In this respect, previous analysis of the ECL is the fundamental step in establishing the ideal site for embryo transfers.

Implantation failures: Success of assisted hatching with quarter-laser zona thinning

Implantation failure after IVF is one of the factors associated with a reduced chance of pregnancy for some patients. Assisted hatching methodologies are designed to facilitate the embryo's escape from the zona pellucida, and this strategy has been suggested as a means of improving pregnancy rates in patients with previous implantation failure. The aim of this prospective and randomized study was to evaluate the efficacy of quarter-laser zona thinning assisted hatching (qLZT-AH) in improving the implantation of embryos in patients with previous implantation failure. A total of 150 patients with a history of previous implantation failure were treated with intracytoplasmic sperm injection, and allocated into two groups: group 1, only one previous implantation failure, and group 2, repeated implantation failures. The patients in each group were randomized at the time of embryo transfer into a control group (no qLZT-AH) or experimental group where qLZT-AH was performed. For patients with repeated implantation failures, the implantation rate in those who received laser-thinned embryos was significantly higher (P=0.02) than in those whose embryos were not laser-thinned (10.9 and 2.6% respectively). However, this difference was not observed in patients who presented with only one previous implantation failure. The data demonstrate that qLZT-AH is an effective strategy for improving the implantation of embryos in patients with repeated implantation failures.

Avaliação da fertilidade e de possíveis defeitos estruturais externos sobre a prole de ratos machos expostos cronicamente ao arsênio

Arsenic is an environmental pollutant that influences the male reproductive function, affecting the spermatogenesis process in the testis and causing alterations in the sperm. The objective of this work was evaluate the reproductive efficiency in adult male rats exposed to arsenic and the possible male-mediated structural malformations. The animal were treated with sodium arsenato (3,6 mg/Kg, i.p.), twice a weak, for 15, 30, 45, 60 or 75 days whereas control received only distilled water. Results have showed a reduced pregnancy rate associated to a decrease in the fertility potencial and to a increase in the preimplantation loss. There was a decrease in the fetal weights, as showed by its average. Malformations rate, postimplantation loss and resorptions were unaffect by treatment. These results suggest that chronic exposure to arsenic provokes reduction on fertility of male rats. Further studies are required to clarify the arsenic effects on male reproductive system and male-mediated effects on progeny.

Implantation sites after embryo transfer into the central area of the uterine cavity

A total of 63 pregnancies (47 singleton, 15 twin, 1 triplet) from intracytoplasmic sperm injection cycles were analysed. In all embryo transfers, the catheter was introduced into the endometrial cavity guided by abdominal ultrasound, with the catheter tip placed at the middle point of the endometrial cavity. Gestational sacs (GS) were located 21-24 days after transfer (gestational age = 5 weeks) by two-dimensional and three-dimensional transvaginal ultrasound. The uterine cavity was divided into three parts: upper, middle and lower. Furthermore, the upper region was subdivided into right, middle and left areas, and the middle region was subdivided into right and left areas. The frequency of gestational sacs in each area was evaluated. In singleton pregnancies 66.0% (31/47) of the GS were detected in the upper region, 29.8% (14/47) in the middle region and 4.2% (2/47) in the lower region. In multiple pregnancies (twins and triplet) 45.5% (15/33) of the GS were detected in the upper region, 51.5% (17/33) in the middle region and 3.0% (1/33) in the lower region. In conclusion, the results demonstrate that when embryos are transferred to the central area of the uterine cavity there is an increase in implantation rate in the middle region compared with the rate expected in naturally conceived pregnancies (9-15%).

Uso da suplementação de LH recombinante na estimulação ovariana com protocolos de FSH recombinante e agonistas do GnRH: Uma revisão da literatura

The purpose of this review was to assess the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in recombinant FSH (r-FSH) and GnRH-agonist (GnRH-a) protocol for IVF/ICSI cycles. Search strategies included on-line surveys of databases from 1990 to 2006. Four trials fulfilled the inclusion criteria (Lisi et al. 2002, Humaidan et al. 2004, Marrs et al. 2004, Tarlatzis et al. 2006). When the review was carried out advantages were observed for the r-LH supplementation protocol with respect to a fewer days of stimulation, a fewer total amount of r-FSH administered and a higher serum estradiol levels on the day of hCG administration. However, these differences were not observed in number of oocyte retrieved, number of mature oocytes, clinical pregnancy per oocyte retrieval, implantation and miscarriage rates. Nevertheless, more randomized controlled trials are necessary before evidence-based recommendations regarding exogenous r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment can be provided.

Laser-assisted hatching of cryopreserved-thawed embryos by thinning one quarter of the zona

Laser-assisted hatching is little documented in the literature regarding its efficacy in cryopreserved-thawed (CT) embryo transfer cycles. The aim of the present study was to evaluate in a randomized manner the efficacy of thinning one quarter of the zona pellucida of CT embryos to a depth of 50-80% of the original thickness, via laser treatment (the qLZT-AH procedure), in improving implantation and pregnancy rates. Two populations were studied: population I, patients who had all their supernumerary embryos cryopreserved, regardless of their morphology, and population II, patients at risk of ovarian hyperstimulation syndrome who had all their embryos cryopreserved. Artificial and natural protocols were used for the embryo transfers. A total of 350 laser-thinned CT embryos were compared with 352 intact zona embryos. No difference in implantation or pregnancy rate was found after using qLZT-AH in either population. These findings suggest that qLZT-AH should not be routinely performed in cryopreserved embryo programmes.

A síndrome do hiperestímulo ovariano não influencia os resultados clínicos após ciclos de descongelamento de embriões provenientes de ciclos de ICSI

Objective: The objective of this study was evaluate if the embryos cryopreservation from OHSS patients Intracytoplasmic Sperm Injection (ICSI) cycles could be influence the clinical outcomes when compared to patients who receive oocytes from donors but the endometrium was not prepared and the embryos were cryopreserved. Methods: Fifty eight couples submitted to ICSI cycles in which 26 with OHSS clinical manifestation (OHSS group) and 32 couples who have received oocytes from donors (control group). The embryos were frozen on day+2 or +3of development. All patients included in this study had embryos crypreserved before the transfer, and in the thawing cycle, only the endometrium preparation was performed. The embryo survival, implantation, pregnancy and miscarriage rates were evaluated in the embryo thawing cycle. Results: There was no difference among the groups in relation to fertilization rate (OHSS: 71.89% ± 15.45, Control: 79.75% ± 21.68, p= 0.234), survival embryos rate (OHSS: 68.85 ± 21.10, Control: 59.53 ± 36.79, p= 0.233), high quality embryos rate (OHSS: 25.20 ± 23.90, Control: 27.40 ± 30.30, p= 0.760), implantation rate (OHSS: 17.9 ± 26.9, Control: 12.5 ± 23.7, p= 0.435), pregnancy rate (OHSS: 38.50, Control: 28.60, p= 0.441) and miscarriage rate (OHSS: 40.00, Control: 25.00, p= 0.332). Conclusion: Our findings suggest that clinical outcomes in freeze and thawing cycles were not affected by the presence of ovarian hyperstimulation syndrome clinical manifestation after controlled ovarian stimulation.

Relevância do assited hatching com laser em um programa de ovo-doação utilizando banco de óvulos criopreservados: Um estudo prospectivo randomizado

Objective: This prospective randomized trial evaluated if there is an improvement in clinical outcomes when assisted hatching is performed in embryos derived from vitrified oocytes in an ovum donation program. Methods: Sixty oocyte recipients undergoing donation program using egg-cryobanking were randomly allocated to the assisted hatched (AH, n=30) or control group (n=30). Pregnancy and implantation rates were compared between the groups. Vitrification and warming procedure were carried out according to the Cryotopmethod. Immediately before embryo transfer, embryos undergoing laser-assisted hatching had the zona pellucida thinned using a 1.48 μm wavelength diode laser. Results: A total of 288 vitrified MII oocytes were warmed for the 60 recipients (4.8 oocytes per recipient). Out of 288 vitrified oocytes, 273 (94.8%) survived. All surviving oocytes were sperm injected and 228 displayed 2 pronucleus 16-18h after injection (83.5%). There were 172 good quality embryos transferred. Twenty four patients achieved clinical pregnancy (total pregnancy rate of 40%). The clinical pregnancy rate did not differ between AH and control groups (44.4% and 33.3%, respectively, p=0.1967), however AH resulted in a significant higher implantation rate (31.6% and 18.4%, p=0.0206). These findings were confirmed by the regression models either for pregnancy (OR = 1.14; IC 95% = 0.80-.72; p= 0.766), as for the implantation rate (RC:19.45, P=0.041). Conclusions: Our evidences demonstrated the effectiveness of the AH in embryos derived from warmed oocytes and suggest that oocyte cryopreservation is a valuable tool to provide successful outcomes in an egg donor program. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Valor preditivo do potencial de implantação embrionário pela análise do perfil químico de meios de cultivo por espectrometria de massas (ESI-Q-ToF)

Objective: This case-control study analyzed mass spectrometry fingerprinting patterns of culture media samples used for embryo culture to predict embryo implantation. Methods: The culture medium harvested after embryo transfer of 22 embryos from 13 patients was used for the experiments. After embryo transfer, the remaining culture media were collected and samples were split in positive (n=8) and negative (n=14) implantation groups according to implantation outcomes (100% or 0% of implantation). Samples were individually diluted and injected directly to the Electrospray ionization (ESI) MS coupled to a Quadrupole Time-of-flight MS (Q-ToF-MS).Ions relative intensities of each spectrum were considered. Data analysis was conducted in MatLab 7.0 version using Partial Least Squares - Discriminant Analysis toolbox. Results: There were 3027 observed ions at 100% and 0% implantation groups by ESI-Q-ToF-MS. The statistical model could categorize the samples in two clusters, based on their positive and negative implantation outcomes. Less intense ions present in the mass spectra with statistical significance have contributed to the major differences to group distinction. Conclusions: Positive and negative implantation embryos showed a specific biochemical pattern present in culture media, which could be detected as a fast, simple and non-invasive way. This biochemical profile could help the selection of the most viable embryo, improving single embryo transfer and thus eliminating the risk and undesirable outcomes of multiple pregnancies. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Revisando os efeitos da concentração de oxigênio sobre o desenvolvimento embrionário

Despite the fact that the processes of embryo development and implantation of mammals do not occur in atmospheric tension in vivo, it is common practice in laboratories for in vitro fertilization (IVF) the culture of embryos in an oxygen tension of 20%. The discrepancy between the tensions of oxygen leads to important discussions about their effects in vitro embryo development. It is believed that the culture of embryo in atmospheric oxygen tension can be detrimental to the quality of the data for predisposing them to the negative interference of reactive oxygen species (ROS), resulting in oxidative stress, leading to deleterious effects on metabolism embryo gene expression and blastocysts grown in those conditions. Faced with arguments for and against the culture of embryos in vitro oxygen tensions similar to those found in vivo, this revies article aims to condense and discuss the literature concerning the influence of oxygen tension on the quality of in vitro culture.

Gewebeprotektive und antiinflammatorische Wirkung von humanem Choriogonadotropin in Mausmodellen mit autoimmunem Leberschaden

Während der Schwangerschaft kommt es häufig zu einer spontanen Verbesserung von klinischen Symptomen der autoimmunen Hepatitis und anderen Th1-vermittelten Autoimmunerkrankungen. Die Gründe hierfür sind bis heute noch nicht vollständig aufgeklärt. Eines der wichtigsten Hormone in der Schwangerschaft ist das humane Choriogonadotropin (hCG), welches schon in der frühen Schwangerschaft eine entscheidende Rolle spielt. Es sorgt für die Stimulation des Corpus luteums, wodurch es zur Ausschüttung von Progesteron kommt und somit die Einnistung der Blastozyte gewährleistet und die Abstoßung des Embryos verhindert wird. In dieser Arbeit wurden Effekt und Signalweg von hCG in primären murinen und humanen Hepatozyten sowie in Mausmodellen mit T-Zell-abhängigem Leberschaden untersucht. hCG führte sowohl bei akuten als auch bei chronischen Leberschäden zu einer drastischen Senkung der Aspartat-Aminotransferase, einem Indikator für Lebererkrankungen. Die Histologie der Leber hCG-behandelter Tiere wies außerdem signifikant weniger apoptotische Zellen und eine deutliche Reduktion infiltrierender CD4+ T-Zellen auf. Die Analyse des hCG-Signalweges zeigte, dass hCG die Langlebigkeitsproteine Foxo3a und Sirt1 reguliert. Die Aktivierung des PI3-Kinase/Akt-Signalweges durch hCG führte zu einem Transport des Transkriptionsfaktors Foxo3a aus dem Zellkern, wodurch die proapoptotischen Zielgene Bim und Puma nicht mehr transkribiert werden können. Eine zusätzliche Hemmung von Foxo3a erfolgte durch die Aktivierung der Deacetylase Sirt1, indem diese phosphoryliert wird und in den Zellkern transloziert. In weiteren Untersuchungen wurde der immunsuppressive Effekt von hCG näher betrachtet. Dabei stellte sich heraus, dass hCG effektiv die proteolytische Aktivität der Caspase-3 in Hepatozyten hemmt, wodurch die Ausschüttung der biologisch aktiven Form von Interleukin-16, einem chemotaktischen Faktor für CD4+ Zellen, herabgesetzt wird. Dadurch wird die Leber erfolgreich vor der Infiltration durch autoaggressive CD4+ Zellen geschützt. IL-16 spielt bei vielen inflammatorischen Krankheiten eine Rolle, was auch in dieser Arbeit durch den Nachweis hoher IL-16-Konzentrationen in Seren von Patienten mit autoimmuner Hepatitis bestätigt werden konnte. Die in dieser Studie beschriebene Wirkung von hCG und die Tatsache, dass hCG ein bereits bewährtes und auf Nebenwirkungen getestetes Medikament bei Infertilität ist, macht es zu einem idealen Kandidaten für immunsuppressive Therapieansätze bei akuten und chronisch entzündlichen Lebererkrankungen.

Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site.

The mechanism(s) that regulates invasion of trophoblasts through the uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.

Abordaje psicoanalítico de la relación madre-hijo durante el embarazo y la forma en que esta afecta el desarrollo psicoafectivo del niño

Resumen Este documento hace una revisión de literatura desde un enfoque psicoanalítico sobre la relación madre – hijo durante el embarazo y la forma en que este influye en el desarrollo psíquico del bebé. Se aborda esta temática principalmente desde la visión teórica de Donald Winnicott, Wilfred Bion y Helene Deutsch para lograr un análisis más integral del vínculo madre-hijo. La elección de autores se hizo teniendo en cuenta que para cada uno de ellos este vínculo constituye una parte fundamental en el desarrollo psicoafectivo del niño, así como la importancia que le dan a la concepción y al embarazo en dicho proceso.