- Email: [email protected]
Relationship of Peritoneal Fluid Oxidative Stress Status and Subsequent Pregnancy in Endometriosis Patients
more recent 3 year period. Lesions most likely to be histologically confirmed endometriosis were ⬎5 mm deep and ⬎10 mm wide. The most common site was the ovarian fossa, while the highest percent of histologically-proven were those on the uterosacral ligaments. As we previously reported, mixed color lesions had the highest likelihood of endometriosis. In contrast to our previous report, black lesions had a higher rate of confirmed endometriosis than white ones. Thus, to surgically treat endometriosis, it is important to identify and remove all types of endometriosis lesions. Supported by: Intramural Program of the National Institute of Child Health and Human Development
Wednesday, October 19, 2005 4:45 p.m. O-302 Marked Expression of Macrophage Migration Inhibitory Factor in the Intrauterine Endometrium of Women With Endometriosis Varying With the Disease Stage, the Infertility Status and Pelvic Pain. A. Akoum, C. N. Metz, R. Kats. Laval University, Quebec, PQ, Canada; NS-LIJ Research Institute, New York, NY. OBJECTIVE: Defined as the ectopic growth of endometrial tissue, endometriosis is a common disease in women of reproductive age frequently associated with pain and infertility. Angiogenesis is a key condition for endometrial tissue to survive and grow in ectopic locations. Recent data from our laboratory identified macrophage migration inhibitory factor (MIF) as a potent angiogenic factor released by ectopic endometrial cells. Our subsequent studies revealed a significant elevation of MIF concentrations in the peritoneal fluid of women with endometriosis, particularly in those who were infertile, and marked expression in active and early stage endometriotic lesions. The objective of the present study was to investigate MIF expression in the eutopic endometrial tissue of women with endometriosis, taking into account endometriosis stage and the infertility status. DESIGN: Retrospective study to examine MIF protein and mRNA expression in endometrial tissue of women with and without endometriosis. MATERIALS AND METHODS: Endometrial biopsies were obtained from 45 women with endometriosis and 55 normal fertile women (controls). MIF expression was assessed by immunohistochemistry, dual immunofluorescence, western blot, ELISA and northern blot. RESULTS: MIF was expressed throughout endometrial tissue, particularly in the glands, endothelial cells and macrophages. In normal fertile women, MIF protein and mRNA expression followed a regulated cycle phase-dependent pattern. MIF levels were markedly higher in women with endometriosis (P ⬍ 0.0001), increased with the disease stage and followed a remarkable cycle-phase dependency. Of note is the significant increase in MIF levels occurring in the mid-secretory phase of the menstrual cycle during the receptive period or what is called the implantation window (P ⬍ 0.05), particularly in infertile patients (P ⬍ 0.01), as well as in the late secretory phase preceding menstruations (P ⬍ 0.001). Furthermore, MIF levels appeared to be particularly elevated in women who were infertile (P ⬍ 0.01) and suffered from pelvic pain (P ⬍ 0.001). CONCLUSION: This study showed a marked increase in MIF concentrations in the intrauterine endometrial tissue of women with endometriosis, occurring at specific moments of the menstrual cycle, a relationship with disease progress and points toward a significant role for this factor in endometriosis-associated pain and infertility. Supported by: Supported by grant MOP-37921 to Ali Akoum from The CIHR. Ali Akoum is a “Chercheur-Boursier National” of the FRSQ. We thank the group of investigation in gynecology, Drs Simon Carrier, Jean-Yves Fontaine, Rodolphe Maheux, Jacques Mailloux and Marc Villeneuve.
wal, T. Falcone, J. M. Goldberg, S. Arrigain, E. Mascha. Cleveland Clinic Foundation, Cleveland, OH. OBJECTIVE: The purpose of this study was to assess whether women with endometriosis, idiopathic infertility, and tubal ligation have different levels of reactive oxygen species (ROS), total antioxidant capacity (TAC), and ROS-TAC score in their peritoneal fluid, and to assess whether the ROS-TAC score is a better predictor of endometriosis and successful pregnancy than the ROS and TAC scores alone. DESIGN: Prospective controlled study MATERIALS AND METHODS: Peritoneal fluid from 108 women: 60 with endometriosis (group I), 38 with tubal ligation/reanastomosis (group II) and 10 with idiopathic infertility (group III) was obtained. ROS was measured by enhanced chemiluminescence assay using luminol as the probe. TAC was measured using the colorimetric assay (Randox Laboratories, Crumlin, UK). ROS-TAC score is calculated by principal components analysis and a score ⬍30 is indicative of high oxidative stress (Sharma et al., 1999). We compared the ability to predict endometriosis and pregnancy by each ROS and TAC versus the ROS-TAC score using DeLong nonparametric method of comparing 2 dependent ROC curves. RESULTS: Groups I and II had significantly higher ROS values than group III (p⫽0.0005). Conversely, the ROS-TAC score was significantly higher in-group III compared with groups I and II (p⫽0.003). Peritoneal fluid TAC levels were comparable in all 3 groups. The area under the curve (AUC) was calculated for each measure to assess its predictive value. The ROS-TAC score (AUC⫽0.71, 95% CI⫽ 0.60, 0.81) was no better at predicting endometriosis diagnosis than either the TAC (AUC⫽0.73, 95% CI⫽ 0.63, 0.82) or ROS (AUC⫽0.73, 95% CI⫽ 0.63, 0.83) levels alone. Of the 54 endometriosis patients attempting to conceive, the 11 who were successful had significantly lower levels of log ROS values (P⫽0.001), higher levels of TAC (P⫽0.02), and higher ROS-TAC scores (P⫽0.002) than endometriosis patients who did not get pregnant. Both pregnant and non-pregnant patients were comparable regarding the age, BMI and gravidity.
*Kruskal-Wallis test followed by Dunn’s multiple comparison procedure when significant aEndometriosis and tubal ligation significantly different from each other bEndometriosis and idiopathic significantly different from tubal ligation
CONCLUSION: Women with endometriosis and idiopathic infertility have significantly lower ROS-TAC scores or higher levels of oxidative stress than a control group of women who underwent tubal ligation/reanastomosis. The high levels of ROS and low levels of TAC could be expressed by the combined ROS-TAC score. Endometriosis patients with lower peritoneal fluid ROS and higher TAC levels are more likely to conceive than others. Supported by: None
Wednesday, October 19, 2005 5:15 p.m. O-304
Wednesday, October 19, 2005 5:00 p.m. O-303
The Effects of Estradiol on the Expression of Estrogen, Progesterone, Androgen, and Prolactin Receptors in Human Peritoneal Fibroblasts. L. Detti, G. M. Saed, H. Lu, Z. Jiang, S. Aboulba, M. P. Diamond. Wayne State University/Detroit Medical Center, Detroit, MI.
Relationship of Peritoneal Fluid Oxidative Stress Status and Subsequent Pregnancy in Endometriosis Patients. M. A. Bedaiwy, A. Agar-
OBJECTIVE: Previous studies have suggested a possible role of hormonal milieu mediating endometriosis and/or postoperative adhesion de-
S124
Abstracts
Vol. 84, Suppl 1, September 2005
Wednesday, October 19, 2005 4:45 p.m. O-302 Marked Expression of Macrophage Migration Inhibitory Factor in the Intrauterine Endometrium of Women With Endometriosis Varying With the Disease Stage, the Infertility Status and Pelvic Pain. A. Akoum, C. N. Metz, R. Kats. Laval University, Quebec, PQ, Canada; NS-LIJ Research Institute, New York, NY. OBJECTIVE: Defined as the ectopic growth of endometrial tissue, endometriosis is a common disease in women of reproductive age frequently associated with pain and infertility. Angiogenesis is a key condition for endometrial tissue to survive and grow in ectopic locations. Recent data from our laboratory identified macrophage migration inhibitory factor (MIF) as a potent angiogenic factor released by ectopic endometrial cells. Our subsequent studies revealed a significant elevation of MIF concentrations in the peritoneal fluid of women with endometriosis, particularly in those who were infertile, and marked expression in active and early stage endometriotic lesions. The objective of the present study was to investigate MIF expression in the eutopic endometrial tissue of women with endometriosis, taking into account endometriosis stage and the infertility status. DESIGN: Retrospective study to examine MIF protein and mRNA expression in endometrial tissue of women with and without endometriosis. MATERIALS AND METHODS: Endometrial biopsies were obtained from 45 women with endometriosis and 55 normal fertile women (controls). MIF expression was assessed by immunohistochemistry, dual immunofluorescence, western blot, ELISA and northern blot. RESULTS: MIF was expressed throughout endometrial tissue, particularly in the glands, endothelial cells and macrophages. In normal fertile women, MIF protein and mRNA expression followed a regulated cycle phase-dependent pattern. MIF levels were markedly higher in women with endometriosis (P ⬍ 0.0001), increased with the disease stage and followed a remarkable cycle-phase dependency. Of note is the significant increase in MIF levels occurring in the mid-secretory phase of the menstrual cycle during the receptive period or what is called the implantation window (P ⬍ 0.05), particularly in infertile patients (P ⬍ 0.01), as well as in the late secretory phase preceding menstruations (P ⬍ 0.001). Furthermore, MIF levels appeared to be particularly elevated in women who were infertile (P ⬍ 0.01) and suffered from pelvic pain (P ⬍ 0.001). CONCLUSION: This study showed a marked increase in MIF concentrations in the intrauterine endometrial tissue of women with endometriosis, occurring at specific moments of the menstrual cycle, a relationship with disease progress and points toward a significant role for this factor in endometriosis-associated pain and infertility. Supported by: Supported by grant MOP-37921 to Ali Akoum from The CIHR. Ali Akoum is a “Chercheur-Boursier National” of the FRSQ. We thank the group of investigation in gynecology, Drs Simon Carrier, Jean-Yves Fontaine, Rodolphe Maheux, Jacques Mailloux and Marc Villeneuve.
wal, T. Falcone, J. M. Goldberg, S. Arrigain, E. Mascha. Cleveland Clinic Foundation, Cleveland, OH. OBJECTIVE: The purpose of this study was to assess whether women with endometriosis, idiopathic infertility, and tubal ligation have different levels of reactive oxygen species (ROS), total antioxidant capacity (TAC), and ROS-TAC score in their peritoneal fluid, and to assess whether the ROS-TAC score is a better predictor of endometriosis and successful pregnancy than the ROS and TAC scores alone. DESIGN: Prospective controlled study MATERIALS AND METHODS: Peritoneal fluid from 108 women: 60 with endometriosis (group I), 38 with tubal ligation/reanastomosis (group II) and 10 with idiopathic infertility (group III) was obtained. ROS was measured by enhanced chemiluminescence assay using luminol as the probe. TAC was measured using the colorimetric assay (Randox Laboratories, Crumlin, UK). ROS-TAC score is calculated by principal components analysis and a score ⬍30 is indicative of high oxidative stress (Sharma et al., 1999). We compared the ability to predict endometriosis and pregnancy by each ROS and TAC versus the ROS-TAC score using DeLong nonparametric method of comparing 2 dependent ROC curves. RESULTS: Groups I and II had significantly higher ROS values than group III (p⫽0.0005). Conversely, the ROS-TAC score was significantly higher in-group III compared with groups I and II (p⫽0.003). Peritoneal fluid TAC levels were comparable in all 3 groups. The area under the curve (AUC) was calculated for each measure to assess its predictive value. The ROS-TAC score (AUC⫽0.71, 95% CI⫽ 0.60, 0.81) was no better at predicting endometriosis diagnosis than either the TAC (AUC⫽0.73, 95% CI⫽ 0.63, 0.82) or ROS (AUC⫽0.73, 95% CI⫽ 0.63, 0.83) levels alone. Of the 54 endometriosis patients attempting to conceive, the 11 who were successful had significantly lower levels of log ROS values (P⫽0.001), higher levels of TAC (P⫽0.02), and higher ROS-TAC scores (P⫽0.002) than endometriosis patients who did not get pregnant. Both pregnant and non-pregnant patients were comparable regarding the age, BMI and gravidity.
*Kruskal-Wallis test followed by Dunn’s multiple comparison procedure when significant aEndometriosis and tubal ligation significantly different from each other bEndometriosis and idiopathic significantly different from tubal ligation
CONCLUSION: Women with endometriosis and idiopathic infertility have significantly lower ROS-TAC scores or higher levels of oxidative stress than a control group of women who underwent tubal ligation/reanastomosis. The high levels of ROS and low levels of TAC could be expressed by the combined ROS-TAC score. Endometriosis patients with lower peritoneal fluid ROS and higher TAC levels are more likely to conceive than others. Supported by: None
Wednesday, October 19, 2005 5:15 p.m. O-304
Wednesday, October 19, 2005 5:00 p.m. O-303
The Effects of Estradiol on the Expression of Estrogen, Progesterone, Androgen, and Prolactin Receptors in Human Peritoneal Fibroblasts. L. Detti, G. M. Saed, H. Lu, Z. Jiang, S. Aboulba, M. P. Diamond. Wayne State University/Detroit Medical Center, Detroit, MI.
Relationship of Peritoneal Fluid Oxidative Stress Status and Subsequent Pregnancy in Endometriosis Patients. M. A. Bedaiwy, A. Agar-
OBJECTIVE: Previous studies have suggested a possible role of hormonal milieu mediating endometriosis and/or postoperative adhesion de-
S124
Abstracts
Vol. 84, Suppl 1, September 2005