Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

Background: Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods: Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results: Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion: Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.Fil: Pisaneschi, Silvia. Università degli Studi di Pisa; Italia. Scuola Superiore Sant’Anna; ItaliaFil: Strigini, Francesca A. L.. Università degli Studi di Pisa; ItaliaFil: Sanchez, Angel Matias. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Begliuomini, Silvia. Università degli Studi di Pisa; ItaliaFil: Casarosa, Elena. Università degli Studi di Pisa; ItaliaFil: Ripoli, Andrea. National Research Council. Institute of Clinical Physiology, ; ItaliaFil: Ghirri, Paolo. Università degli Studi di Pisa; ItaliaFil: Boldrini, Antonio. Università degli Studi di Pisa; ItaliaFil: Fink, Bruno. Noxygen Science Transfer and Diagnostics; AlemaniaFil: Genazzani, Andrea R.. Università degli Studi di Pisa; ItaliaFil: Coceani, Flavio. Scuola Superiore Sant’Anna; ItaliaFil: Simoncini, Tommaso. Università degli Studi di Pisa; Itali

Different stimulation protocols for oocyte cryropreservation in oncological patients: a retrospective analysis of single university centre

Objective: To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer treatment in order to preserve fertility through oocytes cryopreservation. Study design: The study is a retrospective analysis about 25 cancer patients at our centre, Department of Reproductive Medicine of University of Pisa, in order to preserve their fertility before cancer treatment. Patients are divided into two groups depending on the menstrual cycle phase, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is administered in the follicular group, whereas in the second group we use GnRH (gonadotropin-releasing hormone) antagonist before gonadotropins administration in order to have a rapid luteolysis. The outcome measures are the number of days needed before starting procedure, duration of stimulation, cumulative dosage of gonadotropins number of oocyte retrieved and percentage of mature oocytes. Results: Any difference showed between two groups based on days of stimulation, total amount of gonadotropins administered and the number of good mature quality oocytes was retrieved. The real difference is the number of days needed to start the procedure, lesser in the luteal group. Conclusions: This study suggests that oocytes can be obtained before cancer treatment, irrespective of menstrual cycle phase without compromising the efficacy of procedure. Moreover, starting ovarian stimulation anytime during menstrual cycle allows the patients to not postpone the beginning of cancer treatment. Different stimulation protocols, according to different kinds of disease, are available in order to obtain the maximum results without any complication for patient

17-β-estradiol and progesterone serum levels in temporomandibular disorder patients

Considering the hypothesis that some temporomandibular joint (TMJ) tissues could be a potential target for sexual hormones, the aim of the study was to evaluate estrogen (17-beta-estradiol) and progesterone serum levels in a young adult population affected by articular forms of temporomandibular disorders (TMD) versus a control group of healthy subjects. METHODS: A total of 35 patients with Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I Group II diagnosis of disk displacement and/or Group III diagnosis of arthralgia, osteoarthritis or osteoarthrosis, were recruited at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa, Italy, along with a sex- and age-matched group of 24 healthy controls. In all patients, 17-beta-estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) serum levels were determined using a radioimmunoassay. A T-test was performed to compare mean 17-beta-estradiol and progesterone serum levels in the TMD groups with mean serum levels of their respective control groups. Significance was set at p<0.05. RESULTS: Significant differences between patients affected by TMJ disorders and healthy controls were found for serum concentration of 17-beta-estradiol, both in males (p<001) and in the luteal phase of the menstrual cycle in females (p<0.05). No difference was found for progesterone serum levels in the different experimental samples. CONCLUSIONS: The results of this study suggest that high serum estrogens levels might be implicated in the physiopathology of temporomandibular joint disorders, since subjects with these pathologies showed significantly higher serum levels with respect to a group of healthy controls

PCOS and pregnancy: a review of available therapies to improve the outcome of pregnancy in women with polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a common cause of female infertility affecting multiple aspects of a women’s health. Areas covered: The aim of this review is to summarize the existing evidence on the treatment of PCOS patients and to examine the actual available therapies to overcome the problem of infertility and improve the outcome of pregnancy. We analyse different treatment strategies such as lifestyle modification, bariatric surgery, insulin sensitizing agents, inositol, clomiphene citrate (CC), aromatase inhibitors, gonadotrophins, laparoscopic ovarian drilling, and assisted reproductive techniques (ART). Expert commentary: Lifestyle modification is the best initial management for obese PCOS patients seeking pregnancy and insulin sensitizing agents seem to have an important role in treating insulin resistance. Up to now, CC maintains a central role in the induction of ovulation and it has been confirmed as the first-line treatment; the use of gonadotrophins is considered the second-line in CC resistant patients; laparoscopic ovarian drilling is an alternative to gonadotrophins in patients who need laparoscopy for another reason. However, in anovulatory patients, ART represents the only possible alternative to obtain pregnancy. Larger and well-designed studies are needed to clarify the best way to improve the outcome of pregnancy in PCOS women

Follicular fluid VEGF levels directly correlate with perifollicular blood flow in normoresponder patients undergoing IVF

It has become increasingly clear that the follicular microenvironment of the maturing human oocyte is a determining factor for the implantation potential of an embryo deriving from that oocyte. Indeed the quality and maturity of an oocyte are influenced by the level of intrafollicular oxygen content which, in turn, is proportional to the degree of follicular vascularity. The aim of the study was to establish whether there is a relationship between follicular fluid VEGF concentrations, perifollicular vascularity and reproductive outcome in normal responders under the age of 35 undergoing IVF. MATERIALS AND METHODS: Sixty-one consecutive patients, all at their first IVF cycle, were included in the study. All patients had primary infertility due to male factor or tubal factor. At oocyte retrieval, the perifollicular vascularity of two follicles per ovary was estimated qualitatively through power Doppler blood flow, for a total of two hundred forty-four follicles. The follicular fluid from the identified follicles was centrifuged and stored until VEGF assay. The maturity and fertilization rate of the corresponding oocytes as well as embryo quality and pregnancy rate were recorded. RESULTS: In our study, we found VEGF levels to be significantly correlated with grade of perifollicular vascularity. Oocytes obtained from follicles with the higher grade of vascularization also showed a higher rate of fertilization, embryos, a better quality and higher pregnancy rates were obtained in women with highly vascularized follicles. Perifollicular blood flow doppler indices seem to predict oocyte viability and quality. Moreover, VEGF may play a potential role in the development of the perifollicular capillary network. DISCUSSION: The ability of a given follicle to express VEGF and develop an adequate vascular network may be inter-related in patients under the age of 35. An adequate blood supply may be fundamental important in the regulation of intrafollicular oxygen levels and the determination of oocyte quality

Shaman : D14.3 - Report on demonstration and evaluation activity in the domain of industrial design and engineering

1. The report is accounting for the demonstration and evaluation of ISP2, which was designed to demonstrate the potential of the SHAMAN framework for digital preservation in the context of industrial design and engineering companies and for the research and development community.2. The demonstration process was carried out by means of presentation based on screen-casts in Philips Consumer Lifestyle division the Audio, Video, Multimedia and Accessories business area members. They were typical members of a consumer organization and were involved in engineering or middle management work in the company, one was an intern.3. The evaluation is based on the report of a focus group held in Philips‟s Eindhoven headquarters. It is supplemented with structured data from self-completed questionnaires, administered on the same occasions. However, the level of participation in the focus group was low as three out of nine intended participants withdrew because of more pressing duties on the morning of the event. Therefore, the data show only the individual opinions. However, the evaluation methods were successful in delivering useful information for the preparation of this deliverable.4. Participants pointed out that, although their needs for digital preservation were limited, other business areas in the division were more likely to have greater needs, for example, the Health and Wellness area, which had legal obligations to retain data. The theoretical justification for the SHAMAN framework appeared to be of little interest to them. The primary requirement they had of software was that it should „save the time of the engineer‟. The elements resembling the optimum system, i.e., those that accepted a document or design and then automatically extracted all the necessary metadata to enable it to be found and used in the future, were favoured most. The participants found some features of the demonstrator, such as the Open Conjurer module and the concept of „terminology evolution‟ particularly appealing.5. It is quite evident that the SHAMAN framework is applicable to the domain, and it is also evident that the key factors that will make digital preservation in general a requirement will depend very much on the nature of the business. The area of audio and video appliances does not need a very long-term preservation because of the rather short lifetime of an individual product. However, even here, in a different business area, relating to health and well-being, legal requirements necessitate a much longer period of preservation for documents and their need for digital preservation will be much greater.6. Evaluation has also been performed to determine the project‟s impact on the R&amp;D community by means of submission and rejection rates of papers to journals and conferences, and bibliometric and Webometric analyses. The results demonstrate that the research outputs from the project are of interest to the R&amp;D community and that the impact of the project as a whole compares favourably with other European projects in the digital preservation area.7. The evaluation has revealed strengths and shortcomings in the demonstration process, which will influence the further development of demonstrators for all three SHAMAN domains of interest. The SHAMAN framework for digital preservation is seen as offering new possibilities and interesting approaches to information capturing and re-use by the practitioners in industrial design and engineering companies.Sponsorship:EU sjunde ramprogrammet</p

Shaman : D14.3 - Report on demonstration and evaluation activity in the domain of industrial design and engineering

1. The report is accounting for the demonstration and evaluation of ISP2, which was designed to demonstrate the potential of the SHAMAN framework for digital preservation in the context of industrial design and engineering companies and for the research and development community.2. The demonstration process was carried out by means of presentation based on screen-casts in Philips Consumer Lifestyle division the Audio, Video, Multimedia and Accessories business area members. They were typical members of a consumer organization and were involved in engineering or middle management work in the company, one was an intern.3. The evaluation is based on the report of a focus group held in Philips‟s Eindhoven headquarters. It is supplemented with structured data from self-completed questionnaires, administered on the same occasions. However, the level of participation in the focus group was low as three out of nine intended participants withdrew because of more pressing duties on the morning of the event. Therefore, the data show only the individual opinions. However, the evaluation methods were successful in delivering useful information for the preparation of this deliverable.4. Participants pointed out that, although their needs for digital preservation were limited, other business areas in the division were more likely to have greater needs, for example, the Health and Wellness area, which had legal obligations to retain data. The theoretical justification for the SHAMAN framework appeared to be of little interest to them. The primary requirement they had of software was that it should „save the time of the engineer‟. The elements resembling the optimum system, i.e., those that accepted a document or design and then automatically extracted all the necessary metadata to enable it to be found and used in the future, were favoured most. The participants found some features of the demonstrator, such as the Open Conjurer module and the concept of „terminology evolution‟ particularly appealing.5. It is quite evident that the SHAMAN framework is applicable to the domain, and it is also evident that the key factors that will make digital preservation in general a requirement will depend very much on the nature of the business. The area of audio and video appliances does not need a very long-term preservation because of the rather short lifetime of an individual product. However, even here, in a different business area, relating to health and well-being, legal requirements necessitate a much longer period of preservation for documents and their need for digital preservation will be much greater.6. Evaluation has also been performed to determine the project‟s impact on the R&amp;D community by means of submission and rejection rates of papers to journals and conferences, and bibliometric and Webometric analyses. The results demonstrate that the research outputs from the project are of interest to the R&amp;D community and that the impact of the project as a whole compares favourably with other European projects in the digital preservation area.7. The evaluation has revealed strengths and shortcomings in the demonstration process, which will influence the further development of demonstrators for all three SHAMAN domains of interest. The SHAMAN framework for digital preservation is seen as offering new possibilities and interesting approaches to information capturing and re-use by the practitioners in industrial design and engineering companies.Sponsorship:EU sjunde ramprogrammet</p

Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes

Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150â\u80\u93225â\u80\u89UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8â\u80\u9312â\u80\u89mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these ?added values? in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent