- Email: [email protected]
Hypoxia-induced interleukin-6 expression in endometriotic stromal cells
Birmingham, Warwickshire, United Kingdom; cNottingham University Research & Treatment Unit in Reproduction (NURTURE), University of Nottingham, Nottingham, Nottinghamshire, United Kingdom.
extragenital manifestations of endometriosis and surgical treatment options in a multidisciplinary setting.
OBJECTIVE: Little is known about how couples experience living with the common, chronic condition endometriosis and in particular how the uncertain relationship between endometriosis and fertility impacts on plans for parenthood. The UK Endopart study uniquely investigated the impact of endometriosis on women and their male partners. This paper presents findings on fertility decision making and experiences of trying to conceive. DESIGN: The Endopart study was a UK based cross-sectional qualitative study (2012-13). MATERIALS AND METHODS: In-depth, face-to-face, audio-recorded interviews with 22 heterosexual couples living with endometriosis were conducted. Women and their male partners were interviewed separately (n¼44). Principles of systematic sampling were employed to ensure diversity amongst participants regarding age, ethnicity, illness trajectory, and recruitment route. Data were transcribed verbatim and analysed thematically using NVivo computer software, informed by gender-relational theory. RESULTS: Eighteen of 22 couples described endometriosis as affecting their plans to have children. Half (n¼9) had sought and/or received medical treatment or investigations for infertility. The remaining nine couples, though not considered infertile, also described a range of impacts on childbearing including: impacts on decisions about reproductive timing, spacing and numbers of children; use of assisted conception technologies; and loss and disruption associated with unwanted childlessness. ‘Anticipated infertility’ as well as actual involuntary childlessness was a significant source of distress and relationship tension. CONCLUSION: Disruption to childbearing caused by endometriosis impacts on couple relationships in complex ways, not hitherto well acknowledged or understood. Anxiety, uncertainty and anticipated loss are experienced by men and women and should be considered by professionals in the clinical encounter. Supported by: UK Economic and Social Research Council (grant ref: ES/ J003662/1).
P-768 Wednesday, October 16, 2013
P-767 Wednesday, October 16, 2013 COMBINATION VIDEO - ASSISTED THORACOSCOPIC SURGERY AND VIDEO ASSISTED LAPAROSCOPIC SURGERY FOR TREATMENT OF ENDOMETRIOSIS: A MULTIDICIPLINARY APPROACH. J. M. Miller,a C. Paka,a R. Beygui,b C. Nezhat.a aStanford University Hospital, Department of Obstetrics and Gynecology, Center for Special Minimally Invasive and Robotic Surgery, Palo Alto, CA; bStanford University Hospital, Department of Cardiothoracic Surgery, Stanford Cardiothoracic Surgery, Mountain View, CA. OBJECTIVE: To report our experience of systematically combining video – assisted thoracoscopic surgery (VATS) and video – assisted laparoscopic surgery (VALS) for the treatment of abdomino-pelvic, diaphragmatic and thoracic endometriosis. DESIGN: Retrospective study. MATERIALS AND METHODS: We report our experience of systematically combining VATS and VALS for the treatment of abdomino-pelvic, diaphragmatic and thoracic endometriosis. Additionally, information was reviewed as part of clinical follow-up regarding safety and efficacy of combined procedure. RESULTS: Data set includes 19 patients with the average age at time of surgical intervention being 37 years (25 - 60). All patients except one had an extensive history of dysmenorrhea and dyspareunia. Eighty-nine percent had complaints of catamenial chest pain and in 53% this was their only chest complaint. Catamenial pneumothorax was noted in 26%, shoulder pain in 21% and 16% had hemoptysis. Eighty-four percent of patients had undergone previous surgery for treatment of endometriosis. For those who underwent previous surgery for endometriosis, the average time to a combined, multidisciplinary surgical treatment was 10 years from initial surgical diagnosis of endometriosis. Only three out of the 19 cases had no previous diagnosis of endometriosis. Eighty-nine percent of the cases (17) had no major postoperative complications. There was one major thoracic complication and one major pelvic complication. CONCLUSION: Clinical suspicion and preoperative assessment is crucial in the diagnosis of thoracic endometriosis and allows for a multidisciplinary preconsultation. Combination of VATS and VALS for treatment of endometriosis optimally addresses the pelvis, diaphragm and thoracic cavity in a single operation. This case series represents an opportunity to further evaluate
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ASRM Abstracts
EVALUATION OF CELL DIFFERENTIATION AND TISSUE INVASION MARKERS IN TOPIC AND ECTOPIC ENDOMETRIUM IN A RABBIT EXPERIMENTAL MODEL OF V. C. M. Brand~ao,a ENDOMETRIOSIS. J. C. Rosa-e-Silva,a J. Meola,a S. B. Garcia,b O. B. Poli-Neto,a A. A. Nogueira.a aGynecology and Obstetrics, Faculty of Medicine of Ribeir~ao Preto- University of S~ao Paulo, Ribeir~ao Preto, S~ao Paulo, Brazil; bPathology and Legal Medicine, Faculty of Medicine of Ribeir~ao Preto- University of S~ao Paulo, Ribeir~ao Preto, S~ao Paulo, Brazil. OBJECTIVE: To characterize the pattern of differentiation and tissue invasion on topic and ectopic endometrium of rabbits with induced endometriosis, four and eight weeks after the endometrial implantation procedure in order to characterize the histological evolution of the lesions. DESIGN: Prospective experimental model using a rabbit experimental model. MATERIALS AND METHODS: Twenty nine adult New Zealand rabbits, females, virgins, were submitted to laparotomy for lesion induction of endometriosis by resection and suture of a fragment of the right uterine horn (5 x 5mm) in pelvic peritoneum. The rabbits were divided into two groups: group 1, consisted of 14 animals that were sacrificed after 4 weeks of induction of ectopic endometrial lesions and, group 2 comprised 15 animals, with evolution time of eight weeks. The lesion was excised for histological analysis along with the contralateral uterine horn, proving the presence of endometrial glandular and stroma tissue. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissue for analysis of the following markers: metalloprotease 9 (MMP 9) and tissue inhibitor of metalloprotease 2 (TIMP 2), both involved in the invasive capacity of endometrial tissue, and Metallothionein and p63, involved in cell differentiation and proliferation. RESULTS: There was a higher immunostaining for MMP 9, TIMP 2, Metallothionein and p63 in ectopic tissue compared with eutopic endometrium. However, when the ectopic lesions of 4 and 8 weeks were compared no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. CONCLUSION: The ectopic lesions seem to express increased cell differentiation and tissue invasion when compared to eutopic endometrium, featuring endometriosis as a disease potentially invasive, progressive and heterogeneous in its presentation. Supported by: CNPq (Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico). P-769 Wednesday, October 16, 2013 HYPOXIA-INDUCED INTERLEUKIN-6 EXPRESSION IN ENDOJ.-L. Tsai,b METRIOTIC STROMAL CELLS. M-H. Wu,a,b S.-J. Tsai.b aDepartment of Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan; bDepartment of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan. OBJECTIVE: Endometriosis is a common gynecologic disease of reproductive age women. Several cytokines, such as interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor-a, are elevated in peritoneal fluid of women with endometriosis. Hypoxia is also a critical stress during the development and progression of endometriosis. We hypothesized that aberrant expression of IL-6 is under the regulation of HIF-1a in endometriotic stromal cells. DESIGN: This study was designed to investigate the functional role of hypoxia in regulation of IL-6 signaling pathway in endometriosis. MATERIALS AND METHODS: After separation of endometrial specimens, stromal cells were cultured in DMEM/F12 under normoxia or hypoxia, or treated with IL-6. Levels of proteins were detected by Western blotting. RESULTS: The expression of IL-6 was upregulated by hypoxia. Knockdown of dual specificity phosphatase-2 (DUSP2) induced the expression of IL-6. In contrast, forced expression of DUSP2 under hypoxic condition abolished hypoxia-induced IL-6 expression. IL-6 triggered phosphorylation of signal transducer and activator of transcription 3 (STAT3) in endometrial stromal cells. CONCLUSION: Hypoxia-induced IL-6 expression was mediated via downregulation of DUSP2. Aberrant activation of IL-6-STAT3 signaling pathway was due to overexpression of HIF-1a. Our data indicated that
Vol. 100, No. 3, Supplement, September 2013
hypoxia-activated IL-6-STAT3 signaling pathway may involve in the pathogenesis of endometriosis.
P-770 Wednesday, October 16, 2013 DOES ENDOMETRIOSIS CAUSE MITOCHONDRIAL DYSFUNCTION IN CUMULUS CELLS? AN IVF STUDY. A. L. Hsu,a P. M. Birdsall,b S. Oehninger,a F. J. Castora.b aReproductive Endocrinology and Infertility, Jones Institute for Reproductive Medicine, Norfolk, VA; bDepartment of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA. OBJECTIVE: To investigate whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa) cells of patients undergoing IVF. DESIGN: Prospective cohort study. MATERIALS AND METHODS: All women undergoing IVF or oocyte donation at our institution were invited to participate in this IRB-approved study (#13-04-EX-0110) with no exclusion criteria. Subjects with prior laparoscopy were assessed for presence or absence of endometriosis at that surgery, with all others assessed for ultrasound suspicion or symptoms of endometriosis. Controlled ovarian hyperstimulation was conducted using standard protocols. Cumulus cells were stripped from oocytes with hyaluronidase, then analyzed for genomic DNA and mitochondrial DNA (mtDNA) number with qPCR, and for mitochondrial activity by ATP bioluminescent assay, against standard curves. Student t-test or Kruskal-Wallis was used to compare groups. RESULTS: In analyzing patients with surgically-proven endometriosis (n¼9) vs surgical confirmation of no endometriosis (n¼8), there were more ATP per genomic DNA (11.8 vs 8.8 attomoles/DNA molecule, P¼0.4414) and fewer mtDNA per genomic DNA (126.1 vs 149.0, P¼0.2482). In patients with no prior surgery, those with ultrasound findings or symptoms suggestive of endometriosis (n¼19) had significantly fewer ATP per genomic DNA (5.4 vs 8.7 attomoles/DNA molecule, P¼0.0389) despite similar levels of mtDNA per genomic DNA (101.8 vs 99.5, P¼0.3297) compared to patients with no suspicion of endometriosis (n¼32). CONCLUSION: Endometriosis may cause abnormal mitochondrial activity in cumulus cells, as reflected in increased ATP production and fewer mtDNA molecules. Greater ATP production suggests increased metabolic activity, which we speculate could result in increased reactive oxygen species that may inhibit fertility. Our dramatically different findings in patients with no prior surgery but only a clinical suspicion of endometriosis helps to emphasize the importance of restricting endometriosis studies to surgically-proven cases.
P-771 Wednesday, October 16, 2013 ABSTRACT WITHDRAWN
P-772 Wednesday, October 16, 2013 MEDICAL SHRINKAGE OF ENDOMETRIOMAS WITH AROMATASE INHIBITION AND PROGESTIN ADD-BACK. S. K. Agarwala W. G. Foster.b aReproductive Medicine, UC San Diego, La Jolla, CA; bObstetrics and Gynecology, McMaster University, Hamilton, ON, Canada. OBJECTIVE: To assess whether medical therapy with an aromatase inhibitor and progestin add-back could shrink endometriomas. DESIGN: A retrospective analysis of 12 endometriomas treated medically in 7 women. MATERIALS AND METHODS: This study was performed at the University of California, San Diego Center for Endometriosis Research and Treatment. Twelve endometriomas were treated medically in 7 consecutive women with symptomatic endometriosis who were a) not currently trying to conceive and b) wished to preserve fertility for future conception. Consent was obtained for a 3m off-label course of 5mg letrozole with 5mg norethindrone acetate add-back. Pre and post treatment assessments of endometrioma sizes were performed by ultrasound. The mean of the largest two diameters of each endometrioma was recorded. The impact of treatment on pain was determined using the patient assessed endpoints of the Biberoglu and Behrman scale. These included assessing dysmenorrhea, dyspareunia and nonmenstual pelvic pain on a scale of 0 to 3. RESULTS: Mean SD age: 32.4 7.6 years. Mean SD number of prior providers consulted for pelvic pain: 2.3 1.3
Endometrioma diameter mean/cm Endometrioma diameter SD/cm Range of mean endometrioma diameter/cm Mean dysmenorrhea score/3 mean dyspareunia score/3 Mean nonmenstrual pelvic pain score/3
Baseline
3 months
4.6 1.6 1.7 - 7.4 2 1 1
2.3 1.7 0 - 4.3 0 0 0
CONCLUSION: Oocyte retrieval for IVF in women with endometriomas has increased risk of complications and culture contamination with endometriotic fluid. However, excision of endometriomas has been clearly shown to negatively impact ovarian reserve and number of oocytes retrieved for in-vitro fertilization. Medical shrinkage of endometriomas appears to be a viable option for women interested in avoiding surgery for endometiomas. Further study regarding the use of letrozole/ norethindrone acetate for shrinkage of endometriomas prior to IVF is required. Supported by: UC San Diego internal Center for Endometriosis Research and Treatment establishment grant.
P-773 Wednesday, October 16, 2013 NORETHISTERONE ACETATE VERSUS NORETHISTERONE ACETATE COMBINED WITH LETROZOLE FOR THE TREATMENT OF OVARIAN ENDOMETRIOTIC CYSTS: A PATIENT PREFERENCE STUDY. S. Ferrero, V. Remorgida, P. L. Venturini, U. Leone Roberti Maggiore. Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Liguria, Italy. OBJECTIVE: To compare the efficacy of norethisterone acetate (NETA, group N) or NETA and letrozole (group L) in treating endometriotic ovarian cysts. DESIGN: This patient preference study was performed between February 2010 and November 2011 in the University hospital of Genoa, Italy. MATERIALS AND METHODS: Patients with single non-recurrent endometriomas were treated with NETA (2.5 mg/day) or a combination of oral letrozole (2.5 mg/day), norethisterone acetate (2.5 mg/ day), elemental calcium and vitamin D3. The volume of the endometrioma was estimated by using the virtual organ computer-aided analysis (VOCAL, GE Healthcare, Milwaukee, WI, USA). The primary aim of the study was to compare the volume of the endometriotic ovarian cysts during and after treatment and to evaluate the changes in pain symptoms.
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extragenital manifestations of endometriosis and surgical treatment options in a multidisciplinary setting.
OBJECTIVE: Little is known about how couples experience living with the common, chronic condition endometriosis and in particular how the uncertain relationship between endometriosis and fertility impacts on plans for parenthood. The UK Endopart study uniquely investigated the impact of endometriosis on women and their male partners. This paper presents findings on fertility decision making and experiences of trying to conceive. DESIGN: The Endopart study was a UK based cross-sectional qualitative study (2012-13). MATERIALS AND METHODS: In-depth, face-to-face, audio-recorded interviews with 22 heterosexual couples living with endometriosis were conducted. Women and their male partners were interviewed separately (n¼44). Principles of systematic sampling were employed to ensure diversity amongst participants regarding age, ethnicity, illness trajectory, and recruitment route. Data were transcribed verbatim and analysed thematically using NVivo computer software, informed by gender-relational theory. RESULTS: Eighteen of 22 couples described endometriosis as affecting their plans to have children. Half (n¼9) had sought and/or received medical treatment or investigations for infertility. The remaining nine couples, though not considered infertile, also described a range of impacts on childbearing including: impacts on decisions about reproductive timing, spacing and numbers of children; use of assisted conception technologies; and loss and disruption associated with unwanted childlessness. ‘Anticipated infertility’ as well as actual involuntary childlessness was a significant source of distress and relationship tension. CONCLUSION: Disruption to childbearing caused by endometriosis impacts on couple relationships in complex ways, not hitherto well acknowledged or understood. Anxiety, uncertainty and anticipated loss are experienced by men and women and should be considered by professionals in the clinical encounter. Supported by: UK Economic and Social Research Council (grant ref: ES/ J003662/1).
P-768 Wednesday, October 16, 2013
P-767 Wednesday, October 16, 2013 COMBINATION VIDEO - ASSISTED THORACOSCOPIC SURGERY AND VIDEO ASSISTED LAPAROSCOPIC SURGERY FOR TREATMENT OF ENDOMETRIOSIS: A MULTIDICIPLINARY APPROACH. J. M. Miller,a C. Paka,a R. Beygui,b C. Nezhat.a aStanford University Hospital, Department of Obstetrics and Gynecology, Center for Special Minimally Invasive and Robotic Surgery, Palo Alto, CA; bStanford University Hospital, Department of Cardiothoracic Surgery, Stanford Cardiothoracic Surgery, Mountain View, CA. OBJECTIVE: To report our experience of systematically combining video – assisted thoracoscopic surgery (VATS) and video – assisted laparoscopic surgery (VALS) for the treatment of abdomino-pelvic, diaphragmatic and thoracic endometriosis. DESIGN: Retrospective study. MATERIALS AND METHODS: We report our experience of systematically combining VATS and VALS for the treatment of abdomino-pelvic, diaphragmatic and thoracic endometriosis. Additionally, information was reviewed as part of clinical follow-up regarding safety and efficacy of combined procedure. RESULTS: Data set includes 19 patients with the average age at time of surgical intervention being 37 years (25 - 60). All patients except one had an extensive history of dysmenorrhea and dyspareunia. Eighty-nine percent had complaints of catamenial chest pain and in 53% this was their only chest complaint. Catamenial pneumothorax was noted in 26%, shoulder pain in 21% and 16% had hemoptysis. Eighty-four percent of patients had undergone previous surgery for treatment of endometriosis. For those who underwent previous surgery for endometriosis, the average time to a combined, multidisciplinary surgical treatment was 10 years from initial surgical diagnosis of endometriosis. Only three out of the 19 cases had no previous diagnosis of endometriosis. Eighty-nine percent of the cases (17) had no major postoperative complications. There was one major thoracic complication and one major pelvic complication. CONCLUSION: Clinical suspicion and preoperative assessment is crucial in the diagnosis of thoracic endometriosis and allows for a multidisciplinary preconsultation. Combination of VATS and VALS for treatment of endometriosis optimally addresses the pelvis, diaphragm and thoracic cavity in a single operation. This case series represents an opportunity to further evaluate
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ASRM Abstracts
EVALUATION OF CELL DIFFERENTIATION AND TISSUE INVASION MARKERS IN TOPIC AND ECTOPIC ENDOMETRIUM IN A RABBIT EXPERIMENTAL MODEL OF V. C. M. Brand~ao,a ENDOMETRIOSIS. J. C. Rosa-e-Silva,a J. Meola,a S. B. Garcia,b O. B. Poli-Neto,a A. A. Nogueira.a aGynecology and Obstetrics, Faculty of Medicine of Ribeir~ao Preto- University of S~ao Paulo, Ribeir~ao Preto, S~ao Paulo, Brazil; bPathology and Legal Medicine, Faculty of Medicine of Ribeir~ao Preto- University of S~ao Paulo, Ribeir~ao Preto, S~ao Paulo, Brazil. OBJECTIVE: To characterize the pattern of differentiation and tissue invasion on topic and ectopic endometrium of rabbits with induced endometriosis, four and eight weeks after the endometrial implantation procedure in order to characterize the histological evolution of the lesions. DESIGN: Prospective experimental model using a rabbit experimental model. MATERIALS AND METHODS: Twenty nine adult New Zealand rabbits, females, virgins, were submitted to laparotomy for lesion induction of endometriosis by resection and suture of a fragment of the right uterine horn (5 x 5mm) in pelvic peritoneum. The rabbits were divided into two groups: group 1, consisted of 14 animals that were sacrificed after 4 weeks of induction of ectopic endometrial lesions and, group 2 comprised 15 animals, with evolution time of eight weeks. The lesion was excised for histological analysis along with the contralateral uterine horn, proving the presence of endometrial glandular and stroma tissue. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissue for analysis of the following markers: metalloprotease 9 (MMP 9) and tissue inhibitor of metalloprotease 2 (TIMP 2), both involved in the invasive capacity of endometrial tissue, and Metallothionein and p63, involved in cell differentiation and proliferation. RESULTS: There was a higher immunostaining for MMP 9, TIMP 2, Metallothionein and p63 in ectopic tissue compared with eutopic endometrium. However, when the ectopic lesions of 4 and 8 weeks were compared no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. CONCLUSION: The ectopic lesions seem to express increased cell differentiation and tissue invasion when compared to eutopic endometrium, featuring endometriosis as a disease potentially invasive, progressive and heterogeneous in its presentation. Supported by: CNPq (Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico). P-769 Wednesday, October 16, 2013 HYPOXIA-INDUCED INTERLEUKIN-6 EXPRESSION IN ENDOJ.-L. Tsai,b METRIOTIC STROMAL CELLS. M-H. Wu,a,b S.-J. Tsai.b aDepartment of Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan; bDepartment of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan. OBJECTIVE: Endometriosis is a common gynecologic disease of reproductive age women. Several cytokines, such as interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor-a, are elevated in peritoneal fluid of women with endometriosis. Hypoxia is also a critical stress during the development and progression of endometriosis. We hypothesized that aberrant expression of IL-6 is under the regulation of HIF-1a in endometriotic stromal cells. DESIGN: This study was designed to investigate the functional role of hypoxia in regulation of IL-6 signaling pathway in endometriosis. MATERIALS AND METHODS: After separation of endometrial specimens, stromal cells were cultured in DMEM/F12 under normoxia or hypoxia, or treated with IL-6. Levels of proteins were detected by Western blotting. RESULTS: The expression of IL-6 was upregulated by hypoxia. Knockdown of dual specificity phosphatase-2 (DUSP2) induced the expression of IL-6. In contrast, forced expression of DUSP2 under hypoxic condition abolished hypoxia-induced IL-6 expression. IL-6 triggered phosphorylation of signal transducer and activator of transcription 3 (STAT3) in endometrial stromal cells. CONCLUSION: Hypoxia-induced IL-6 expression was mediated via downregulation of DUSP2. Aberrant activation of IL-6-STAT3 signaling pathway was due to overexpression of HIF-1a. Our data indicated that
Vol. 100, No. 3, Supplement, September 2013
hypoxia-activated IL-6-STAT3 signaling pathway may involve in the pathogenesis of endometriosis.
P-770 Wednesday, October 16, 2013 DOES ENDOMETRIOSIS CAUSE MITOCHONDRIAL DYSFUNCTION IN CUMULUS CELLS? AN IVF STUDY. A. L. Hsu,a P. M. Birdsall,b S. Oehninger,a F. J. Castora.b aReproductive Endocrinology and Infertility, Jones Institute for Reproductive Medicine, Norfolk, VA; bDepartment of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA. OBJECTIVE: To investigate whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa) cells of patients undergoing IVF. DESIGN: Prospective cohort study. MATERIALS AND METHODS: All women undergoing IVF or oocyte donation at our institution were invited to participate in this IRB-approved study (#13-04-EX-0110) with no exclusion criteria. Subjects with prior laparoscopy were assessed for presence or absence of endometriosis at that surgery, with all others assessed for ultrasound suspicion or symptoms of endometriosis. Controlled ovarian hyperstimulation was conducted using standard protocols. Cumulus cells were stripped from oocytes with hyaluronidase, then analyzed for genomic DNA and mitochondrial DNA (mtDNA) number with qPCR, and for mitochondrial activity by ATP bioluminescent assay, against standard curves. Student t-test or Kruskal-Wallis was used to compare groups. RESULTS: In analyzing patients with surgically-proven endometriosis (n¼9) vs surgical confirmation of no endometriosis (n¼8), there were more ATP per genomic DNA (11.8 vs 8.8 attomoles/DNA molecule, P¼0.4414) and fewer mtDNA per genomic DNA (126.1 vs 149.0, P¼0.2482). In patients with no prior surgery, those with ultrasound findings or symptoms suggestive of endometriosis (n¼19) had significantly fewer ATP per genomic DNA (5.4 vs 8.7 attomoles/DNA molecule, P¼0.0389) despite similar levels of mtDNA per genomic DNA (101.8 vs 99.5, P¼0.3297) compared to patients with no suspicion of endometriosis (n¼32). CONCLUSION: Endometriosis may cause abnormal mitochondrial activity in cumulus cells, as reflected in increased ATP production and fewer mtDNA molecules. Greater ATP production suggests increased metabolic activity, which we speculate could result in increased reactive oxygen species that may inhibit fertility. Our dramatically different findings in patients with no prior surgery but only a clinical suspicion of endometriosis helps to emphasize the importance of restricting endometriosis studies to surgically-proven cases.
P-771 Wednesday, October 16, 2013 ABSTRACT WITHDRAWN
P-772 Wednesday, October 16, 2013 MEDICAL SHRINKAGE OF ENDOMETRIOMAS WITH AROMATASE INHIBITION AND PROGESTIN ADD-BACK. S. K. Agarwala W. G. Foster.b aReproductive Medicine, UC San Diego, La Jolla, CA; bObstetrics and Gynecology, McMaster University, Hamilton, ON, Canada. OBJECTIVE: To assess whether medical therapy with an aromatase inhibitor and progestin add-back could shrink endometriomas. DESIGN: A retrospective analysis of 12 endometriomas treated medically in 7 women. MATERIALS AND METHODS: This study was performed at the University of California, San Diego Center for Endometriosis Research and Treatment. Twelve endometriomas were treated medically in 7 consecutive women with symptomatic endometriosis who were a) not currently trying to conceive and b) wished to preserve fertility for future conception. Consent was obtained for a 3m off-label course of 5mg letrozole with 5mg norethindrone acetate add-back. Pre and post treatment assessments of endometrioma sizes were performed by ultrasound. The mean of the largest two diameters of each endometrioma was recorded. The impact of treatment on pain was determined using the patient assessed endpoints of the Biberoglu and Behrman scale. These included assessing dysmenorrhea, dyspareunia and nonmenstual pelvic pain on a scale of 0 to 3. RESULTS: Mean SD age: 32.4 7.6 years. Mean SD number of prior providers consulted for pelvic pain: 2.3 1.3
Endometrioma diameter mean/cm Endometrioma diameter SD/cm Range of mean endometrioma diameter/cm Mean dysmenorrhea score/3 mean dyspareunia score/3 Mean nonmenstrual pelvic pain score/3
Baseline
3 months
4.6 1.6 1.7 - 7.4 2 1 1
2.3 1.7 0 - 4.3 0 0 0
CONCLUSION: Oocyte retrieval for IVF in women with endometriomas has increased risk of complications and culture contamination with endometriotic fluid. However, excision of endometriomas has been clearly shown to negatively impact ovarian reserve and number of oocytes retrieved for in-vitro fertilization. Medical shrinkage of endometriomas appears to be a viable option for women interested in avoiding surgery for endometiomas. Further study regarding the use of letrozole/ norethindrone acetate for shrinkage of endometriomas prior to IVF is required. Supported by: UC San Diego internal Center for Endometriosis Research and Treatment establishment grant.
P-773 Wednesday, October 16, 2013 NORETHISTERONE ACETATE VERSUS NORETHISTERONE ACETATE COMBINED WITH LETROZOLE FOR THE TREATMENT OF OVARIAN ENDOMETRIOTIC CYSTS: A PATIENT PREFERENCE STUDY. S. Ferrero, V. Remorgida, P. L. Venturini, U. Leone Roberti Maggiore. Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Liguria, Italy. OBJECTIVE: To compare the efficacy of norethisterone acetate (NETA, group N) or NETA and letrozole (group L) in treating endometriotic ovarian cysts. DESIGN: This patient preference study was performed between February 2010 and November 2011 in the University hospital of Genoa, Italy. MATERIALS AND METHODS: Patients with single non-recurrent endometriomas were treated with NETA (2.5 mg/day) or a combination of oral letrozole (2.5 mg/day), norethisterone acetate (2.5 mg/ day), elemental calcium and vitamin D3. The volume of the endometrioma was estimated by using the virtual organ computer-aided analysis (VOCAL, GE Healthcare, Milwaukee, WI, USA). The primary aim of the study was to compare the volume of the endometriotic ovarian cysts during and after treatment and to evaluate the changes in pain symptoms.
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