Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotrophin-releasing hormone agonist

The objective of this study was to evaluate the Doppler flow variations which occur following the use of different protocols of ovarian stimulation in an IVF programme, and to investigate the thromboxane production by cultured endometrial cells and its influence on embryo implantation. A total of 60 patients underwent three different ovarian stimulation protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler analysis were performed before and during the treatment. On the day that the Doppler examination took place, luteinizing hormone, follicle stimulating hormone, plasma oestradiol and thromboxane concentrations were assayed. On the day of oocyte retrieval, endometrial cells were collected and cultured, and their thromboxane production evaluated. No significant differences in hormonal, ultrasonographic or Doppler parameters were observed between the three groups. Ten out of 56 patients who had a successful embryo transfer became pregnant. In the group of pregnant women the pulsatility index values of both uterine and spiral arteries was lower than in non-pregnant patients, and was associated with significantly lower thromboxane concentrations from cultured endometrial cells. It is concluded that thromboxane plays a role in embryo implantation, and that Doppler flow analysis of uterine and spiral arteries in infertile patients may be important in the management of ovarian stimulation.      

Comparison of complications after Ahmed versus Baerveldt implant in glaucoma patients: one year follow-up

AIM: To compare surgical results of the Ahmed and Baerveldt implant procedures in glaucoma patients at 1y follow-up at Jakarta Eye Center (JEC) Eye Hospitals. METHODS: This cohort retrospective study was conducted on glaucoma patients aged ≥18y who had undergone Ahmed and Baerveldt implant surgery. Intraocular pressure (IOP), visual acuity, glaucoma medication, success rate, early and late postoperative complications, and the number of resurgeries were analyzed. RESULTS: A total of 351 eyes in the Ahmed group and 94 eyes in the Baerveldt group were included in this study. At 1y follow-up, the mean IOP was found to be significantly lower in the Baerveldt group (13±4.47 mm Hg) compared to the Ahmed group (15.02±5.73 mm Hg; P=0.025). Glaucoma medication was required in both the Ahmed and Baerveldt groups (58.92% vs 71.67%). Comparable success rate was found in both groups. The Ahmed group revealed a complete and qualified success of 86.82%, and failure of 13.17%. Similarly, the Baerveldt group showed complete and qualified success in 87.75% and failure in 12.25% cases. In the Ahmed group, 11.97% early complications, 26.06% late complications and 9.97% resurgeries were observed. In comparison, in the Baerveldt group, 23.40% early complications, 30.95% late complications and 11.70% resurgeries were observed. CONCLUSION: Both groups of glaucoma implants show significant IOP reduction, however, the Baerveldt implant group demonstrates greater IOP reduction with more failure rates and complications than the Ahmed implant group.     

Brain derived neurotrophic factor circulating levels in patients undergoing IVF

Purpose The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. Methods Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). Results There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. Conclusion Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period. Capsule BDNF plasma concentrations are not predictive of IVF outcome, however they are highly correlated to estradiol levels and seem to be implicated in periovulatory processes.     

Vascular endothelial growth factor, interleukin-6 and interleukin-2 in serum and follicular fluid of patients with ovarian hyperstimulation syndrome

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.     

Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.     

Two-component protein-engineered physical hydrogels for cell encapsulation

Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol–gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from ≈9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.     

Vascular endothelial growth factor and basic fibroblast growth factor in polycystic ovary syndrome during controlled ovarian hyperstimulation.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that causes anovulation and consequent subfertility. It is well established that increased ovarian mass, supported by new blood vessel proliferation in stroma and theca, is a key feature of PCOS. Recent studies suggest a role for angiogenetic factors in this phenomenon. AIM: To evaluate of levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum and follicular fluid of PCOS patients during a controlled ovarian hyperstimulation. METHODS: In 52 patients undergoing in vitro fertilization treatments, 26 PCOS patients and 26 controls, serum VEGF and bFGF levels were assessed before starting administration of follicle-stimulating hormone (FSH) (day 0), on the day of administration of human chorionic gonadotropin (hCG) and on the day of oocyte retrieval. Follicular fluid levels of the two growth factors were detected on the day of oocyte retrieval. RESULTS: PCOS patients showed higher serum VEGF levels than controls before starting FSH administration, on the day of hCG administration and on the day of oocyte retrieval. Serum VEGF levels showed a rise after hCG administration only in the PCOS patients. In addition, serum bFGF levels were higher in PCOS patients than in controls on the day of hCG administration and the day of oocyte retrieval. Furthermore, on the day of hCG administration, serum bFGF levels were directly correlated to the amount of FSH previously administered (p < 0.0001). In follicular fluid, higher VEGF and bFGF levels were found in PCOS patients than in controls. Furthermore, follicular-fluid bFGF concentrations were inversely correlated with the percentage of mature oocytes collected (p < 0.05). CONCLUSIONS: The present study revealed elevated levels of VEGF and bFGF in serum and follicular fluid in PCOS patients compared with controls. bFGF seems to be an FSH-dependent growth factor and its levels in follicular fluid are inversely correlated with the percentage of mature oocytes collected.