Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent

Vascularization is a prominent event during corpus luteum formation, providing low density lipoproteins for steroid biosynthesis and enabling transport of secreted steroids. The process of vascularization is controlled by specific regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular permeability factor (VPF), induces endothelial cell proliferation as well as angiogenesis in vivo and increases capillary permeability. Here we report the expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day 10 was reduced to approximately 30% of the value at day 4. However, after culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of VEGF/VPF mRNA by GC was four times greater than control experiments by day 10, and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results suggest that vascularization of the corpus luteum is induced by HCG-mediated effects of VEGF/VPF.      

Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles

In order to assess the efficacy and safety of recombinant humanfollicle stimulating hormone (FSH) in routine clinical use,ovarian stimulation with recombinant human FSH was performedin 71 patients prior to in-vitro fertilization (IVF) withoutgonadotrophin-releasing hormone (GnRH) analogues in a multicentre,non-comparative study. Human chorionic gonadotrophin (HCG) wasadministered to 58 patients (81.7%), 15 of whom underwent 19cycles with an initial dosage of three ampoules daily of recombinantFSH and 43 of whom underwent 152 cycles with four ampoules dailyfrom day 3 onwards. No significant differences were detectedbetween these two groups in all test parameters. The mean durationof treatment was 9.06 and 8.86 days respectively with a meannumber of 24.06 and 23.25 vials of recombinant human FSH administered.A mean number of 6.26 and 5.88 oocytes respectively was collected.The number of transferred embryos was 2.4 and 2.2. A clinicalpregnancy rate of 23.8% (10 out of 42) per transfer was achieved(30.9 and 20.6% respectively). Local tolerance of s.c. administrationwas excellent. Mild pain at the injection site was the dominantfinding in <20% of patients. Two cases of ovarian hyperstimulationsyndrome were noted. Recombinant human FSH is very attractiveto patients because it can be self-administered s.c. and thepreparation does not come from a human source. In conclusion,these data support the safety and efficacy of recombinant humanFSH in routine use for IVF.     

Image guidance to improve reliability and data integrity of transcranial Doppler sonography

Background

Principles and accuracy of image-guided transcranial Doppler (IG TCD) sonography have been published recently. However, it remains open whether combination of image guidance and TCD offers an additional clinical advantage. This study scores the accuracy of conventional TCD examinations and investigates the potential improvement of TCD data integrity and reliability regarding the additional use of IG.

Methods

Conventional TCD was performed by a group of experienced investigators, who were blinded to images of a navigation system tracking the Doppler probe, whereas an independent observer documented the TCD findings, acquired by the investigators, due to saving spatial data of the TCD sample volume using IG for subsequent analysis. In a second set of experiments, image guidance was available to investigators without any previous TCD experience.

Results

The analysis of 3D data of vessels (n = 173) labeled by experienced investigators in conventional TCD, revealed a rate of 37% misinterpreted Doppler signals regarding the target vessel. Correctness of labeling was comparable between the different vascular segments. The rate of correct labeling was higher for right- (69%) than for left-sided vessels (57%). In comparison, by using IG, TCD investigators without any previous TCD experience achieved a significantly lower rate of 10% (n = 39) mislabeled vessels.

Conclusions

Our data suggest, that misinterpretation of the vascular source of the Doppler signal is a common source of errors in conventional TCD. Visualization of the vascular anatomy by image guidance offers improved accuracy and reliability of TCD results and may positively influence the learning curve for inexperienced investigators.     

Post-partum acquired haemophilia after IVF without recurrence during a second pregnancy obtained by IVF

Sir, We were highly interested in the case report published by Nakauchi-Tanakaet al. (2003), reporting a factor VIII inhibitor in ovarianhyperstimulation syndrome (OHSS). Briefly, acquired haemophilia is a rare disease most often dueto the development of autoantibodies directed against factorVIII that interfere with its coagulant function. The incidenceis about 1 per million persons per year. Acquired haemophiliamay occur in association with autoimmune diseases such as systemiclupus erythematosus or rheumatoid arthritis, neoplastic diseases,drug hypersensitivity and pregnancy. However, 50% of the casesremain idiopathic. Post-partum factor VIII inhibitors most oftendisappear     

ProstaglandinProduktion (PGF2alpha,PGE2) in menschlichen Granulosazellen in vitro

Ohne Zusammenfassung     

Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure

OBJECTIVE: Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro. STUDY DESIGN: BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation, Bcl-2, and caspase 7 expression. RESULTS: In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis, whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bcl-2 and cytokeratin 18 protein expression. Heparin and aspirin inhibited DNA laddering. CONCLUSION: Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss.     

Cytosol and nuclear progesterone-receptor concentrations in the rabbit endometrium during early pseudopregnancy under different treatments with estradiol and progesterone

In an attempt to understand the mechanism of the antiprogestational action of estrogens during early pseudopregnancy we determined the cytosolic and nuclear concentrations of progesterone receptors in the endometrium of rabbits treated with hCG followed by various combinations of estradiol and progesterone. The progestational response of the endometrium was followed by quantitation of the uteroglobin content in the uterine lumen.In rabbits treated with hCG alone there was a clear progestational response (40% relative uteroglobin content), but only 16% of the progesterone receptors were located in the nucleus.After additional treatment with progesterone the progestational response remained high (45% relative uteroglobin content), the total cellular content of progesterone receptor increased, and 5% of the complexes were found in the nucleus. These findings suggest that a consumption of nuclear progesterone receptor is required for progestational action.Treatment of pseudopregnant rabbits with estradiol resulted in a marked increase not only of the total cellular progesterone receptor but also of the percentage of it located in the nucleus (35%). Concomitantly, the progestational response was markedly inhibited (5% relative uteroglobin content). These results confirm the relevance of nuclear consumption of progesterone receptor for progestational action, and suggest that some antiprogestational effects of estrogens may be due to their interference with the mechanism of progesterone receptor processing.