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Endocrine and immune systems are among the most essential regulators of endometrial physiology, and immune-endocrine interactions are likely to be involved in the pathogenesis of endometriosis. Endometriosis is an inflammatory, estrogen-dependent disease defined by the presence of viable endometrial tissue outside the uterine cavity. Impaired immune response that results in inadequate removal of refluxed menstrual debris has been proposed as a possible causative factor in the development of endometriosis. Moreover, decrease in spontaneous apoptosis of endometrium is the other theory proposed for the development of endometriosis. Endometriotic tissues respond to sex steroids aberrantly and behave differently compared to endometrium in addition to their ability to produce local estrogen. The effects of estrogen on distinct intracellular signaling pathways including MAPK, PI3K/AKT and NF-kappa B may take a role in enhanced endometrial cell survival, altered immune response, and differential cytokine and chemokine expression in endometriosis. Better understanding of immune-endocrine interactions will set the stage for effective immune-targeted therapies not only for endometriosis but also for other endometrial diseases such as adenomyosis, recurrent reproductive failure and implantation-related infertility. more...

Objective: To evaluate the role of sonohysterography for screening of the uterine cavity in patients with recurrent pregnancy loss. Design: Prospective evaluation of sonohysterography, including comparison with available hysterosalpingography and hysteroscopy. Setting: University referral center. Patient(s): Thirty-four reproductive-aged women with at least two consecutive pregnancy losses. Intervention(s): Sonohysterography was performed on all patients, using saline instilled through an endocervically placed balloon catheter with concurrent vaginal sonography. Result(s): Seventeen of 34 sonohysterograms (50.0%) demonstrated intrauterine abnormalities. Eighteen of 34 cases have undergone hysteroscopy or, in 1 case, laparoscopy. All confirmed the positive or negative sonohysterography finding, resulting in a sensitivity and specificity of 100%. Additionally, 100% (12/12) of the defects were diagnosed accurately at sonohysterography when confirmed by surgery. Twenty-seven of 34 patients also had a hysterosalpingogram that demonstrated a 90.0% sensitivity and 20.0% specificity based on hysteroscopic findings, yet only 5 of 11 (45.5%) defects were diagnosed accurately at hysterosalpingography when compared with surgery. Conclusion(s): Sonohysterography is a highly sensitive, specific, and accurate screening tool for the evaluation of uterine cavitary defects associated with recurrent pregnancy loss and offers several advantages over hysterosalpingography. more...

OBJECTIVE: To compare the ovarian stimulation characteristics of the new follitropin alfa filled by mass (r-hFSH-fbm) vs. the conventional follitropin alfa filled by bioassay (r-hFSH-bio) in the same egg donor patients. DESIGN: Retrospective observational MATERIALS AND METHODS: From our egg donor program we identified 9 donors who had two egg retrieval cycles, one with r-hFSH-bio (Gonal-f Multidose ®) and other one with r-hFSH-fbm (Gonal-f RFF ®), acting as their own control, for a total of 18 cycles. The protocol of ovarian stimulation was exactly the same in both cycles consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with r-hFSH alfa. Data collected comprised of age, BMI, total days and total amount of r-hFSH, E2 levels at hCG, follicular numbers and diameters, number of oocytes retrieved, fertilized, cleavage and embryo quality. Data was analyzed by JMP 5.0 software with paired T-test for continuous variables and Chi-square test for categorical data as appropriate; significance was set up at p 0.05. RESULTS: The results summarized in the table are expressed as mean standard deviation. The Estradiol peak was statistically higher with the r-hFSH-fbm than with r-hFSH-bio (2,887 vs 2361 pg/ml) (p 0.05). The total amount of FSH utilized, the number of follicles 14 mm, oocytes retrieved, eggs fertilized, cleavage embryos and the total number of embryos at day 3 or 5, showed a positive trend in favor of r-hFSH-fbm , although the differences did not reach statistical significance. more...

Objective: PTEN/MMAC (phosphatase and tensin homologue/mutated in multiple advanced cancers) is a novel tumor suppressor protein. PTEN regulates cell growth, invasion and apoptosis. When PTEN is phosphorylated, its degradation and activity are inhibited. Homozygosity for PTEN gene mutation causes defective placentation and developmental delay, and results in embryonal lethality on day E9.5. The heterozygosity for PTEN gene mutation induces endometrial tumors suggesting a fundamental role for PTEN in endometrial proliferation and early pregnancy in mice. We hypothesized that PTEN has a temporal and spatial expression model throughout the menstrual cycle and during early pregnancy, and progesterone regulates PTEN by affecting either its expression and/or phosphorylation. Design: PTEN expression was studied in normal human endometrial and decidual tissues. Its regulation by progesterone was investigated in cultured human endometrial stromal cells. Materials/Methods: Paraffin and frozen section were obtained from clinically normal endometrium (n 18) and from clinically normal decidua (n 10) of early pregnancies voluntarily terminated by dilation and curettage. To investigate the effect of progesterone on PTEN level and on its phosphorylation, normal and phosphorylated (phospho-PTEN) forms of PTEN were evaluated using Western blot analysis in endometrial stromal cell cultures. Cells were treated with progesterone (10 9 M) for 5 to 30 min to evaluate the short-term effect and for 6–24 h to evaluate the long-term effect on PTEN levels. GAPDH immunoblot analysis was carried out to verify equal loading of proteins. Statistical analysis was done using Student s t-test. Results: Immunohistochemical results revealed that stromal cells had a stronger immunoreactivity for PTEN than glandular cells throughout the menstrual cycle. The immunoreactivity for PTEN was stronger during early proliferative and late secretory phases in both stromal and glandular cells compared to other cycle phases. On the other hand, among the groups, the strongest immunoreactivity was observed in both glandular and decidual cells during early pregnancy with a gradual increase as pregnancy progressed (P 0.05). Both PTEN and phospho-PTEN protein expression were detected in endometrial stromal cells in vitro. Short-term treatment of cells with progesterone decreased both PTEN and phospho-PTEN levels when compared to vehicle (control). PTEN and phospho-PTEN levels were found 23 % and 19 % lower, respectively, in endometrial stromal cells exposed to progesterone for 30 min as compared to vehicle. Interestingly, long-term treatment of cells with progesterone for 6 to 24 h upregulated PTEN and phospho-PTEN levels up to 75 % and 30 %, respectively. Conclusions: Our results showed that PTEN has a specific temporal and spatial expression model in endometrium and decidua throughout the menstrual cycle and early pregnancy, and is likely to be regulated by ovarian hormones. Progesterone-mediated regulation of PTEN supports this finding. Furthermore, progesterone is likely to regulate the PTEN pool by decreasing its phosphorylation in shortterm and increasing protein level in long-term. We conclude that regulation of PTEN may be one of the pathways that progesterone is acting to affect endometrial cell proliferation and/or apoptosis. Supported by: None provided. more...

When Fas ligand (FasL) interacts with the Fas receptor, it induces apoptosis through autocrine and/or paracrine signalling. Vascular endothelial growth factor (VEGF) is a potent mitogenic cytokine. VEGF plays a role during remodelling of the endometrium following menstruation. We hypothesized that, by regulating FasL expression, VEGF may play a role in endometrial stromal cell survival by decreasing autocrine apoptotic signalling. We aimed to determine the expression of FasL in cultured endometrial stromal cells and its modulation by VEGF. VEGF induced a decrease in both FasL-positive cell number and FasL intensity as determined by immunocytochemistry and western blot respectively (P < 0.05). These effects of VEGF were observed in a concentration-dependent manner (10-42%; P < 0.05). Anti-VEGF neutralizing antibody alone resulted in an increase in the FasL expression. When combined with VEGF, anti-VEGF reversed the VEGF-induced decrease in FasL level up to 100% (P < 0.05). In addition, western blot analysis showed that FasL expression in endometrial stromal cells demonstrated a cyclic change every 12 h during 48 h of incubation. These results suggest that down-regulation of FasL by VEGF may affect endometrial stromal cell survival in an autocrine or paracrine manner. The decrease in FasL level may be due to a stimulation of its degradation. Our results show that FasL in endometrial stromal cells in culture has a cyclic expression model, suggesting that there may be a regulation at the translation level. more...

The skill requirements for microlaparoscopy are significantly higher than those for the traditional technique. This program was designed to meet the demands of compensated two-dimensional depth perception, instrument accuracy, and ambidexterity. Three specialized drills were constructed and 60 experienced laparoscopists with advanced operative skills were evaluated. The three skill-assessment tasks were first performed using traditional laparoscopic instrumentation (10-mm laparoscopes, 5-mm accessory instruments). The performance of the study group was compared with an extensive database of over 1000 laparoscopic surgeons from around the world and did not reveal any significant deficits with traditional-size equipment. Next, the tasks were performed using miniature 2-mm laparoscopes and accessory instruments. Performance levels for all tasks were significantly lower than with traditional-size equipment. These results demonstrate the increased difficulty of performing laparoscopy with 2-mm instruments and underscore the importance of formal training and objective skill assessment. The relationship of skill to credentialing must be considered. more...