High Pressure Quenched Glasses: unique structures and properties.

Zr-based metallic glasses are prepared by quenching supercooled liquid under pressure. These glasses are stable in ambient conditions after decompression. The High Pressure Quenched glasses have a distinct structure and properties. The pair distribution function shows redistribution of the Zr-Zr interatomic distances and their shift towards smaller values. These glasses exhibit higher density, hardness, elastic modulus, and yield stress. Upon heating at ambient pressure, they show volume expansion and distinct relaxation behavior, reaching an equilibrated state above the glass transition. These experimental results are consistent with an idea of pressure-induced low to high density liquid transition in the supercooled melt.

Curie-Weiss behavior of liquid structure and ideal glass state.

We present the results of a structural study of metallic alloy liquids from high temperature through the glass transition. We use high energy X-ray scattering and electro-static levitation in combination with molecular dynamics simulation and show that the height of the first peak of the structure function, S(Q) - 1, follows the Curie-Weiss law. The structural coherence length is proportional to the height of the first peak, and we suggest that its increase with cooling may be related to the rapid increase in viscosity. The Curie temperature is negative, implying an analogy with spin-glass. The Curie-Weiss behavior provides a pathway to an ideal glass state, a state with long-range correlation without lattice periodicity, which is characterized by highly diverse local structures, reminiscent of spin-glass.

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. RESULTS: Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV 550.8%) and 78.2% at 200 mg twice daily (Elaris EMIV 575.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.5% at 150 mg once daily (Elaris EM-IV 566.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV 567.2%)."After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. CONCLUSION: Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760954 and NCT02143713.

Stabilization of Polar Nanoregions in Pb-free Ferroelectrics.

The formation of polar nanoregions through solid-solution additions is known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nanoregions (PNR), understanding their real-space atomic structure and dynamics of their formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nanoregions in the Pb-free ferroelectric of Ba(Zr,Ti)O_{3}. It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomic displacements for ferroelectric polarization are slowed sufficiently below THz frequencies, which leads to increased local correlation among dipoles within PNRs. The dynamic pair distribution function technique demonstrates a unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties.

Pressure Induced Liquid-to-Liquid Transition in Zr-based Supercooled Melts and Pressure Quenched Glasses.

Through high-energy x-ray diffraction and atomic pair density function analysis we find that Zr-based metallic alloy, heated to the supercooled liquid state under hydrostatic pressure and then quenched to room temperature, exhibits a distinct glassy structure. The PDF indicates that the Zr-Zr distances in this glass are significantly reduced compared to those quenched without pressure. Annealing at the glass transition temperature at ambient pressure reverses structural changes and the initial glassy state is recovered. This result suggests that pressure causes a liquid-to-liquid phase transition in this metallic alloy supercooled melt. Such a pressure induced transition is known for covalent liquids, but has not been observed for metallic liquids. The High Pressure Quenched glasses are stable in ambient conditions after decompression.

Observation of dynamic atom-atom correlation in liquid helium in real space.

Liquid 4He becomes superfluid and flows without resistance below temperature 2.17 K. Superfluidity has been a subject of intense studies and notable advances were made in elucidating the phenomenon by experiment and theory. Nevertheless, details of the microscopic state, including dynamic atom-atom correlations in the superfluid state, are not fully understood. Here using a technique of neutron dynamic pair-density function (DPDF) analysis we show that 4He atoms in the Bose-Einstein condensate have environment significantly different from uncondensed atoms, with the interatomic distance larger than the average by about 10%, whereas the average structure changes little through the superfluid transition. DPDF peak not seen in the snap-shot pair-density function is found at 2.3 Å, and is interpreted in terms of atomic tunnelling. The real space picture of dynamic atom-atom correlations presented here reveal characteristics of atomic dynamics not recognized so far, compelling yet another look at the phenomenon.

Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS: We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS: A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS: Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).

Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density.

This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: -0.11%/-0.47%, elagolix 75 mg: -1.29%/-1.2%, and DMPA-SC: 0.99%/-1.29% in the spine and total hip, respectively), with similar or less changes at week 48 (posttreatment). Elagolix was associated with improvements in endometriosis-associated pain, assessed with composite pelvic signs and symptoms score (CPSSS) and visual analogue scale, including statistical noninferiority to DMPA-SC in dysmenorrhea and nonmenstrual pelvic pain components of the CPSSS. The most common adverse events (AEs) in elagolix groups were headache, nausea, and nasopharyngitis, whereas the most common AEs in the DMPA-SC group were headache, nausea, upper respiratory tract infection, and mood swings. This study showed that similar to DMPA-SC, elagolix treatment had minimal impact on BMD over a 24-week period and demonstrated similar efficacy on endometriosis-associated pain.

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study.

OBJECTIVE: The aim of this study was to estimate the efficacy of elagolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of endometriosis-associated pelvic pain. METHODS: This was a phase II, randomized, placebo-controlled parallel group study conducted at 37 US centers, consisting of an 8-week double-blind period followed by a 16-week open-label period. Patients were 137 women aged 18 to 49, with laparoscopically confirmed endometriosis and moderate to severe nonmenstrual pelvic pain and dysmenorrhea, who were administered elagolix 150 mg daily or placebo. The primary outcomes of the study were the daily assessment of dysmenorrhea, nonmenstrual pelvic pain and dyspareunia using a modified Biberoglu-Behrman scale. RESULTS: During the double-blind period, there were significantly greater mean reductions from baseline to week 8 in dysmenorrhea (-1.13 ± 0.11 vs. -0.37 ± 0.11, p<0.0001), nonmenstrual pelvic pain (-0.47 ± 0.07 vs. -0.19 ± 0.07, p = 0.0066), and dyspareunia scores (-0.61 ± 0.10 vs. -0.23 ± 0.10, p = 0.0070) in the elagolix group compared with placebo. Continued improvements were observed during the open-label treatment regardless of initial treatment allocation. Elagolix treatment was also associated with significant improvements in quality-of-life measures during the double-blind and open-label periods. The most common adverse events occurring with elagolix were nausea, headache and hot flush, each in 9.9% of patients. CONCLUSION: Elagolix effectively reduced endometriosis-associated pelvic pain over a 24-week period and was well-tolerated.

Elastic heterogeneity in metallic glasses.

When a stress is applied on a metallic glass it deforms following Hook's law. Therefore it may appear obvious that a metallic glass deforms elastically. Using x-ray diffraction and anisotropic pair-density function analysis we show that only about 3/4 in volume fraction of metallic glasses deforms elastically, whereas the rest of the volume is anelastic and in the experimental time scale deform without resistance. We suggest that this anelastic portion represents residual liquidity in the glassy state. Many theories, such as the free-volume theory, assume the density of defects in the glassy state to be of the order of 1%, but this result shows that it is as much as a quarter.

Successful pregnancies after oocyte cryopreservation with slow-freezing method: a report of 3 cases.

BACKGROUND: The technology for successful oocyte cryopreservation has evolved only over the past decade. Fewer than 300 pregnancies achieved with cryopreserved oocytes were reported as of the end of 2006. Two cryopreservation techniques are currently available: the slow-cooling method and vitrification. This article reviews the world literature on pregnancies conceived from cryopreserved oocytes and reports 3 such pregnancies conceived with a slow-cooling method in our facility. CASES: Three patients who underwent in vitro fertilization/embryo transfer cycles had the supranumerary oocytes cryopreserved using a slow-cooling method. After a period of 2-7 months, the oocytes were thawed, fertilized and the resulting embryos were transferred. All 3 patients conceived and 2 delivered-1 singleton and 1 a set of twins. The third patient conceived twins and was in the third trimester of her pregnancy at this writing. Literature review indicates that the majority of pregnancies to date have been achieved with a slow-cooling protocol. However, recent advances in the vitrification technology have improved its effectiveness and because of its simplicity made it the method of choice in oocyte cryopreservation. CONCLUSION: Both slow-freezing and vitrification methods for oocyte cryopreservation can be used effectively to achieve pregnancies. Vitrification is technically simpler and may be more effective than slow freezing.

Local lattice dynamics and the origin of the relaxor ferroelectric behavior.

Relaxor ferroelectricity is observed in many strongly disordered ferroelectric solids. However, the atomistic mechanism of the phenomenon, particularly at high temperatures, is not well understood. In this Letter we show the local lattice dynamics as the origin of relaxor ferroelectricity through the first use of the dynamic pair-density function determined by pulsed neutron inelastic scattering. For a prototypical relaxor ferroelectric, Pb(Mg(1/3)Nb(2/3))O(3), we demonstrate that the dynamic local polarization sets in around the so-called Burns temperature through the interaction of off-centered Pb ions with soft phonons, and the slowing down of local polarization with decreasing temperature produces the polar nanoregions and the relaxor behavior below room temperature.

Immunohistochemical detection of heparanase-1 expression in eutopic and ectopic endometrium from women with endometriosis.

OBJECTIVE: To investigate the expression of heparanase-1, an endoglycosidase that degrades heparan sulfate proteoglycans, in eutopic and ectopic endometrial tissues from women with endometriosis. DESIGN: An immunohistochemical study. SETTING: Academic research laboratory and a private infertility clinic affiliated with a university medical center. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of heparanase-1 analyzed by immunohistochemical staining in 91 eutopic and 14 ectopic endometrial specimens. RESULT(S): We found that 17% (4/24) of the eutopic endometrial specimens in the early proliferative phase and 32% (9/28) of the samples in the midproliferative phase were heparanase-1 positive. However, >or=80% of eutopic endometrial specimens at late proliferate phase and at luteal phase were heparanase-1 positive. Twelve of 14 ectopic endometriotic specimens stained heparanase-1 positive. Comparison of heparanase-1 expression in paired eutopic and ectopic endometrial tissues revealed that 5 of 6 ectopic specimens in the early proliferative phase were heparanase-1 positive, whereas only 1 eutopic specimen was heparanase-1 positive. In comparison with our recent study of heparanase-1 expression in normal endometrium, we found that there was no significant difference in heparanase-1 expression in the eutopic endometrium from women with or without endometriosis. CONCLUSION(S): Heparanase-1 was differentially expressed in the eutopic endometrium in the different menstrual phases. Heparanase-1 was highly expressed in the ectopic endometriotic lesions regardless of their menstrual phases, suggesting that the local environment is responsible for increased heparanase-1 expression.

Estradiol induces heparanase-1 expression and heparan sulphate proteoglycan degradation in human endometrium.

BACKGROUND: This study seeks to determine whether estrogen is able to regulate the expression of heparanase-1 (HPR1) in human endometrium. METHODS: HPR1 expression and heparan sulphate (HS) deposition in the endometrium collected in various menstrual phases were analysed by immunohistochemical and immunofluorescence staining, respectively. HPR1 expression in the endometrial cells unexposed or exposed to estradiol was analysed by using RT-PCR and luciferase reporter assay. HPR1 activity was analysed by using a novel enzyme-linked immunosorbent assay (ELISA). Cell surface HS levels were analysed by flow cytometry. Serum HPR1 activity in women receiving follicle-stimulating hormone (FSH) for IVF was measured by ELISA. RESULTS: HPR1 expression was rarely detected in the endometrium in the early and mid-proliferative phases but was increased in the late proliferative phase and in the secretory phases. HPR1 expression was negatively associated with HS in the basement membrane (BM) of the endometrial glands. HPR1 gene expression, HPR1 promoter activity and HPR1 enzymatic activity were increased in the endometrial cells when exposed to 17beta-estradiol (E(2)), whereas cell surface HS levels showed a decrease which could be blocked by PI-88, an HPR1 inhibitor. Serum HPR1 levels were increased in women with moderately elevated blood estrogen levels after receiving FSH. CONCLUSIONS: HPR1 is differentially expressed in the endometrium in different menstrual phases. Estrogen plays an important role in inducing HPR1 expression, subsequently leading to HS degradation on the endometrial cell surface and in the BM of the endometrium.

Quantitative expression of apoptosis-regulating genes in endometrium from women with and without endometriosis.

OBJECTIVE: To quantitate antiapoptotic and proapoptotic gene expression in endometrial cells (ECs) of women with and without endometriosis. DESIGN: Determination of transcript abundance (TA) of apoptosis-regulating genes in eutopic and ectopic endometrial cells. SETTING: Institute for the Study and Treatment of Endometriosis, Chicago, Illinois, and university-based research laboratories. PATIENT(S): Women with (n = 10) and without (n = 6) endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative virtually multiplexed transcript abundance measurement (VMTA) of the BCL2, BCLxL, defender against cell death-1 (DAD-1), BCLxS, P53, Caspase-1, and proliferating cell nuclear antigen (PCNA) genes. RESULT(S): The TA ratio of antiapoptotic to proapoptotic isoforms of the BCL-X gene favors survival in eutopic and ectopic ECs from women with endometriosis, but not control ECs. This was found throughout the menstrual cycle for ectopic ECs. Eutopic but not ectopic ECs also expressed increased TA of the antiapoptotic DAD-1 gene in endometriosis. Eutopic and ectopic ECs from women with endometriosis expressed decreased TA of p53 and Caspase-1 compared to ECs from women without endometriosis. Expression of these genes was not correlated with the proliferative state of ECs based on TA of the PCNA gene. CONCLUSION(S): Dysregulation in expression of pro- and antiapoptotic regulatory genes characterizes eutopic and ectopic ECs from women with endometriosis. These results are consistent with apoptotic resistance and enhanced survival of ECs in endometriosis.

Direct observation of the formation of polar nanoregions in Pb(Mg1/3Nb2/3)O3 using neutron pair distribution function analysis.

Using neutron pair distribution function analysis over the temperature range from 1000 to 15 K, we demonstrate the existence of local polarization and the formation of medium-range, polar nanoregions (PNRs) with local rhombohedral order in a prototypical relaxor ferroelectric Pb(Mg(1/3)Nb(2/3))O3. We estimate the volume fraction of the PNRs as a function of temperature and show that this fraction steadily increases from 0% to a maximum of approximately 30% as the temperature decreases from 650 to 15 K. Below T approximately 200 K the volume fraction of the PNRs becomes significant, and PNRs freeze into the spin-glass-like state.

Improved outcome of frozen-thawed blastocyst transfer with Menezo's two-step thawing compared to the stepwise thawing protocol.

PURPOSE: To compare the effects of two different blastocyst thawing protocols on implantation, pregnancy, and live birth rates. METHODS: Ninety four consecutive frozen-thawed blastocyst transfers from 1996 to 2002 were retrospectively analyzed. Blastocysts were cryopreserved using Menezo's two-step slow freezing protocol. Frozen blastocysts were thawed for transfer according to Menezo's stepwise or two-step protocol. Immediately after thawing, assisted hatching was performed and all embryos were cultured for 3 to 5 h before transfer. Only viable embryos were selected for transfer. RESULTS: Implantation, pregnancy (determined by the presence of fetal cardiac activity), and live birth rates were significantly higher with two-step (25, 45.7, and 42.9%) than with stepwise thawing protocol (9.2,18.6, and 16.9%, P < 0.01). The percentage of gestational sacs resulting in live babies was higher with two-step thawing (76.6%) than with stepwise thawing (50%, P = 0.04). CONCLUSIONS: We conclude that the two-step thawing protocol offers advantages over the stepwise method. The two-step thawing protocol dramatically increased embryo implantation potential, resulting in higher pregnancy rate, and subsequent live birth rate, after frozen blastocyst transfer.

Immunology of endometriosis.

Endometriosis is a benign gynecologic disorder characterized by the ectopic growth of misplaced endometrial cells. A unifying hypothesis to explain endometriosis has not been elucidated as yet but numerous investigations have implicated disturbances in the immune response as fundamental to its etiology and pathogenesis. Clearly, the immune system is involved in endometriosis. It is not clear, however, whether and to what extent this involvement is a primary response leading to the initiation, promotion, and progression of the disease or a secondary response to the ectopic endometrial growth in an attempt to restore homeostasis. Thus, although numerous studies have shown alterations in cell-mediated and humoral immunity in subjects with endometriosis, the importance of these changes remains obscure. This review considers the past two decades of investigation of immune function changes in women with endometriosis with the expectation that this information will ultimately provide the basis for developing new approaches to patient management.

Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis.

OBJECTIVE: To determine the effect of autologous peritoneal fluid and tumor necrosis factor-alpha (TNF-alpha) on proliferation of endometrial cells from women with endometriosis. DESIGN: Endometrial cells from eutopic and ectopic endometrium were cultured in vitro with peritoneal fluids or recombinant TNF-alpha for 72 hours before DNa synthesis determination by 3H-thymidine labeling and liquid scintillation counting. SETTING: An institute for the study and treatment of endometriosis and university-based research laboratories. PATIENT(S): Thirty-five women with endometriosis and 17 controls without endometriosis. MAIN OUTCOME MEASURE(S): In vitro incorporation of 3H-thymidine in endometrial cells was examined. RESULT(S): Peritoneal fluid from women with endometriosis enhanced proliferation of autologous and heterologous endometrial cell cultures from women with endometriosis. The soluble TNF-receptor etanercept blocked the ability of peritoneal fluid from women with endometriosis to enhance proliferation of eutopic or ectopic endometrial cells. Recombinant TNF-alpha also enhanced proliferation of eutopic and ectopic endometrial cells from women with endometriosis. In contrast, autologous peritoneal fluid, heterologous peritoneal fluid from women with endometriosis, and recombinant TNF-alpha failed to enhance, and often inhibited, the proliferation of eutopic endometrial cells from controls without endometriosis. CONCLUSION(S): Endometrial cells from women with endometriosis can utilize factors in peritoneal fluids, such as TNF-alpha, to facilitate proliferation in ectopic environments. Endometrial cells from women without endometriosis do not share this ability, suggesting that this abnormality is etiologically related to development of the disease. Therapy with agents that block the effects of TNF-alpha may be warranted.