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Ghrelin administration ameliorates adhesion formation in a mouse surgical model
P-198 Tuesday, October 20, 2015 EVALUATION OF OVARIAN RESERVE BEFORE AND AFTER SURGERY IN WOMEN WITH OVARIAN ENDOMETRIOMA COMPARED TO PELVIC ENDOMETRIOSIS AND NEGATIVE CONTROLS: A PROSPECTIVE COHORT TRIAL. L. R. Goodman, J. M. Goldberg, R. Flyckt, M. Gupta, N. Gueye, k. J. Holoch, T. Falcone. Cleveland Clinic, Cleveland, OH. OBJECTIVE: To determine the impact of surgical excision of endometriosis and endometrioma compared with controls on ovarian reserve. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Women aged 18-43 years presenting with pelvic pain and/or infertility undergoing surgical management of suspected endometriosis or endometrioma between October 2013 and April 2015. Patients were excluded if they had prior ovarian surgery. Statistical analysis included student t-tests, paired t-tests and ANOVA where appropriate. RESULTS: A total of 116 patients were included with 58 suspected endometriomas and 58 controls with suspected pelvic endometriosis but no evidence of ovarian involvement on pelvic imaging. All surgeries were performed laparoscopically. All of the suspected endometriomas were completely removed by cystectomy and confirmed by pathology. Of the 58 controls, 31 had biopsy confirmed pelvic endometriosis and 27 patients had no evidence of endometriosis on laparoscopy with pathology negative for endometriosis on biopsy. We prospectively evaluated ovarian reserve measured by Anti-Mullerian Hormone (AMH) prior to surgery, at one month and six months post-operatively. Age, body mass index and proportion of patients with pain and/or infertility did not differ significantly between groups. Table 1: Means (95% Confidence Intervals), { } are p-values compared to preoperative value. Endometrioma (n ¼ 56)
Pelvic Endometriosis (n ¼ 31)
Negative Laparoscopy (n ¼ 27)
P-Value
Age (years) 31.5 (30.1 - 33.3) 31.1 (28.9 - 33.3) 30.9 (28.8 - 33.1) 0.55 Length of 119.8 (105.8 - 128.1) 87.7 (72.6 - 102.7) 69.7 (53.6 - 85.9) <0.01 surgery (min) Pre-operative 1.6 (1.1 - 2.0) 2.2 (1.2 - 3.1) 2.9 (1.6 - 4.2) 0.06 AMH (ng/ml) Post-operative 1.2 (0.8-1.6) {0.05} 2.2 (1.2 - 3.3) {0.70} 2.8 (1.5 - 4.0) {0.54} 0.04 AMH (ng/ml) 6 months Post-op 1.1 (0.5 - 1.7) {0.05} 2.5 (1.5 - 3.5) {0.24} 3.8 (1.5 - 6.2) {0.12} 0.01 AMH (ng/ml)
Overall, baseline AMH values were negatively correlated with age (r ¼ -0.5, p < 0.01). Baseline AMH values were significantly lower in the endometrioma vs. negative laparoscopy group (p ¼0.02), but there was not a significant difference between other groups (endometrioma vs. pelvic endometriosis p ¼ 0.27; pelvic endometriosis vs. negative laparoscopy p ¼ 0.24). There was no difference in pre- and post-operative AMH values in the pelvic endometriosis and negative laparoscopy groups, but patients with endometrioma(s) had a significant decline in ovarian reserve that persisted over the six month period (-25.0% at post-operative visit, -31.2% at 6 month visit; p ¼ 0.05). The rate of AMH decline was positively correlated with baseline pre-op AMH values (r ¼ 0.37, p <0.01) and length of surgery (r ¼ 0.23, p ¼ 0.03), but not with age, laterality, or endometrioma size. CONCLUSIONS: At baseline, patients with endometrioma(s) had significantly lower AMH values when compared to women without endometriosis. Surgical treatment of pelvic endometriosis with no ovarian involvement had no effect on AMH values; however, surgical excision of endometrioma appears to have long-lasting detrimental effects on ovarian reserve. P-199 Tuesday, October 20, 2015 GHRELIN ADMINISTRATION AMELIORATES ADHESION FORMATION IN A MOUSE SURGICAL MODEL. E. Bianchi,a M. Sigman,b K. Boekelheide,c S. J. Hall,c K. Hwang.a aDivision of Urology, Brown University, Providence, RI; bBrown University and Lifespan, Providence, RI; cDepartment of Pathology & Laboratory Medicine, Brown University, Providence, RI. OBJECTIVE: Postoperative intra-abdominal and pelvic adhesions are a leading cause of infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, the endogenous ligand for the growth hor-
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ASRM Abstracts
mone-secretagogue receptor, plays an important role in preventing post-operative adhesions. The purpose of this study is to develop a new experimental adhesion mouse model to evaluate the effectiveness of ghrelin in reducing intraperitoneal adhesions and to define the molecular mechanisms by which ghrelin impacts the prevention of adhesion formation. DESIGN: C57BL/6 wild type mice and growth hormone secretagogue receptor-KO (GHSR KO) mice underwent a midline laparotomy to establish a new post-operative mouse adhesion model. The mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 days after surgery. MATERIALS AND METHODS: We developed a new reproducible experimental mouse method of post-operative adhesions characterized by the combination of cecal multiple abrasion and peritoneal ischemic buttons in wild type and GHSR KO mice. All mice were sacrificed at 21 days after surgery and adhesions were objectively scored by one surgeon using an established scoring system. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson’s trichrome, Picrosirius red stain and Western blot analysis) and gene expression of pro-fibrotic and pro-inflammatory factors by RT-PCR array. RESULTS: Ghrelin administration significantly reduced the number of post-operative adhesions and collagen deposition in the peritoneal ischemic button in wild type mice. The anti-adhesion effect of ghrelin seen in wild type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. Gene expression analysis showed that ghrelin led to a reduction in Il4, Tgfb3 and Tgfbr2 mRNA levels in peritoneal ischemic tissue in wild type mice. No significant difference was detected in ghrelin-treated GHSR KO mice. CONCLUSIONS: These findings indicate that ghrelin administration may improve surgical outcomes by reducing peritoneal adhesion formation in a GHSR-1a dependent manner. Ghrelin may be a candidate therapeutic drug for post-operative adhesion prevention attenuating the inflammatory reaction at the onset of surgery. Supported by: ASRM and Lifespan Hospital. P-200 Tuesday, October 20, 2015 CLINICAL OUTCOMES FOLLOWING OFFICE-BASED ULTRASOUND-GUIDED VS HOSPITAL-BASED LAPAROSCOPY-GUIDED HYSTEROSCOPIC SEPTUM RESECTION IN THE INFERTILE POPULATION. B. Alkudmani,a,b S. Rangarajan,c C. Librach,a,b P. Sharma.a,b aCreate Fertility Center, Toronto, ON, Canada; bUniversity of Toronto, Toronto, ON, Canada; cUniversity of Toronto, Mississauga, ON, Canada. OBJECTIVE: A septate uterus is a congenital uterine malformation resulting from a defect in canalization of the fused midline between the embryologic m€ullerian ducts. Although it can be easily corrected through hysteroscopic septum resection, few studies have assessed the clinical outcomes following the use of ultrasound-guided versus conventional laparoscopic-guided procedures. The objective of this study was to assess whether there is a difference in efficacy between office-based ultrasound-guided hysteroscopic septum resection and a hospital-based laparoscopic-guided approach with regards to procedure outcomes (complications and need for repeat procedures) and pregnancy outcomes (implantation and pregnancy rate). DESIGN: A retrospective cohort study was conducted by evaluating charts of patients at our clinic (n¼58) that underwent hysteroscopic septum resection between 2007 and 2014. MATERIALS AND METHODS: 29 patients having undergone the procedure in hospital under general anesthesia with laparoscopic guidance and 29 patients having undergone an ultrasound guided office-based procedure at the Create Fertility Centre under conscious sedation were included. Data related to patient demographics, complications, need for repeat procedure, pregnancy outcomes, and scheduling were analyzed. RESULTS: Demographic variables were similar between the two groups. There were no statistical differences with regards to procedure and pregnancy outcomes when comparing the ultrasound- versus laparoscopic-guided approach. Specifically, there were no significant differences in complication rate (p¼0.16), need for repeat procedures (p¼0.35), implantation rate (p¼0.06) and pregnancy rate (p¼0.38) after adjusting for sperm quality, AMH, and age. CONCLUSIONS: Transabdominal ultrasound guidance during hysteroscopic septum resection exhibits similar procedure and pregnancy outcomes compared to the laparoscopic approach, with the added benefit of increased safety (sedation vs. GA; no need for laparoscopy), reduced waiting time, and reduced costs (no need for hospital resources or an anesthetist).
Vol. 104, No. 3, Supplement, September 2015
Pelvic Endometriosis (n ¼ 31)
Negative Laparoscopy (n ¼ 27)
P-Value
Age (years) 31.5 (30.1 - 33.3) 31.1 (28.9 - 33.3) 30.9 (28.8 - 33.1) 0.55 Length of 119.8 (105.8 - 128.1) 87.7 (72.6 - 102.7) 69.7 (53.6 - 85.9) <0.01 surgery (min) Pre-operative 1.6 (1.1 - 2.0) 2.2 (1.2 - 3.1) 2.9 (1.6 - 4.2) 0.06 AMH (ng/ml) Post-operative 1.2 (0.8-1.6) {0.05} 2.2 (1.2 - 3.3) {0.70} 2.8 (1.5 - 4.0) {0.54} 0.04 AMH (ng/ml) 6 months Post-op 1.1 (0.5 - 1.7) {0.05} 2.5 (1.5 - 3.5) {0.24} 3.8 (1.5 - 6.2) {0.12} 0.01 AMH (ng/ml)
Overall, baseline AMH values were negatively correlated with age (r ¼ -0.5, p < 0.01). Baseline AMH values were significantly lower in the endometrioma vs. negative laparoscopy group (p ¼0.02), but there was not a significant difference between other groups (endometrioma vs. pelvic endometriosis p ¼ 0.27; pelvic endometriosis vs. negative laparoscopy p ¼ 0.24). There was no difference in pre- and post-operative AMH values in the pelvic endometriosis and negative laparoscopy groups, but patients with endometrioma(s) had a significant decline in ovarian reserve that persisted over the six month period (-25.0% at post-operative visit, -31.2% at 6 month visit; p ¼ 0.05). The rate of AMH decline was positively correlated with baseline pre-op AMH values (r ¼ 0.37, p <0.01) and length of surgery (r ¼ 0.23, p ¼ 0.03), but not with age, laterality, or endometrioma size. CONCLUSIONS: At baseline, patients with endometrioma(s) had significantly lower AMH values when compared to women without endometriosis. Surgical treatment of pelvic endometriosis with no ovarian involvement had no effect on AMH values; however, surgical excision of endometrioma appears to have long-lasting detrimental effects on ovarian reserve. P-199 Tuesday, October 20, 2015 GHRELIN ADMINISTRATION AMELIORATES ADHESION FORMATION IN A MOUSE SURGICAL MODEL. E. Bianchi,a M. Sigman,b K. Boekelheide,c S. J. Hall,c K. Hwang.a aDivision of Urology, Brown University, Providence, RI; bBrown University and Lifespan, Providence, RI; cDepartment of Pathology & Laboratory Medicine, Brown University, Providence, RI. OBJECTIVE: Postoperative intra-abdominal and pelvic adhesions are a leading cause of infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, the endogenous ligand for the growth hor-
e174
ASRM Abstracts
mone-secretagogue receptor, plays an important role in preventing post-operative adhesions. The purpose of this study is to develop a new experimental adhesion mouse model to evaluate the effectiveness of ghrelin in reducing intraperitoneal adhesions and to define the molecular mechanisms by which ghrelin impacts the prevention of adhesion formation. DESIGN: C57BL/6 wild type mice and growth hormone secretagogue receptor-KO (GHSR KO) mice underwent a midline laparotomy to establish a new post-operative mouse adhesion model. The mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 days after surgery. MATERIALS AND METHODS: We developed a new reproducible experimental mouse method of post-operative adhesions characterized by the combination of cecal multiple abrasion and peritoneal ischemic buttons in wild type and GHSR KO mice. All mice were sacrificed at 21 days after surgery and adhesions were objectively scored by one surgeon using an established scoring system. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson’s trichrome, Picrosirius red stain and Western blot analysis) and gene expression of pro-fibrotic and pro-inflammatory factors by RT-PCR array. RESULTS: Ghrelin administration significantly reduced the number of post-operative adhesions and collagen deposition in the peritoneal ischemic button in wild type mice. The anti-adhesion effect of ghrelin seen in wild type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. Gene expression analysis showed that ghrelin led to a reduction in Il4, Tgfb3 and Tgfbr2 mRNA levels in peritoneal ischemic tissue in wild type mice. No significant difference was detected in ghrelin-treated GHSR KO mice. CONCLUSIONS: These findings indicate that ghrelin administration may improve surgical outcomes by reducing peritoneal adhesion formation in a GHSR-1a dependent manner. Ghrelin may be a candidate therapeutic drug for post-operative adhesion prevention attenuating the inflammatory reaction at the onset of surgery. Supported by: ASRM and Lifespan Hospital. P-200 Tuesday, October 20, 2015 CLINICAL OUTCOMES FOLLOWING OFFICE-BASED ULTRASOUND-GUIDED VS HOSPITAL-BASED LAPAROSCOPY-GUIDED HYSTEROSCOPIC SEPTUM RESECTION IN THE INFERTILE POPULATION. B. Alkudmani,a,b S. Rangarajan,c C. Librach,a,b P. Sharma.a,b aCreate Fertility Center, Toronto, ON, Canada; bUniversity of Toronto, Toronto, ON, Canada; cUniversity of Toronto, Mississauga, ON, Canada. OBJECTIVE: A septate uterus is a congenital uterine malformation resulting from a defect in canalization of the fused midline between the embryologic m€ullerian ducts. Although it can be easily corrected through hysteroscopic septum resection, few studies have assessed the clinical outcomes following the use of ultrasound-guided versus conventional laparoscopic-guided procedures. The objective of this study was to assess whether there is a difference in efficacy between office-based ultrasound-guided hysteroscopic septum resection and a hospital-based laparoscopic-guided approach with regards to procedure outcomes (complications and need for repeat procedures) and pregnancy outcomes (implantation and pregnancy rate). DESIGN: A retrospective cohort study was conducted by evaluating charts of patients at our clinic (n¼58) that underwent hysteroscopic septum resection between 2007 and 2014. MATERIALS AND METHODS: 29 patients having undergone the procedure in hospital under general anesthesia with laparoscopic guidance and 29 patients having undergone an ultrasound guided office-based procedure at the Create Fertility Centre under conscious sedation were included. Data related to patient demographics, complications, need for repeat procedure, pregnancy outcomes, and scheduling were analyzed. RESULTS: Demographic variables were similar between the two groups. There were no statistical differences with regards to procedure and pregnancy outcomes when comparing the ultrasound- versus laparoscopic-guided approach. Specifically, there were no significant differences in complication rate (p¼0.16), need for repeat procedures (p¼0.35), implantation rate (p¼0.06) and pregnancy rate (p¼0.38) after adjusting for sperm quality, AMH, and age. CONCLUSIONS: Transabdominal ultrasound guidance during hysteroscopic septum resection exhibits similar procedure and pregnancy outcomes compared to the laparoscopic approach, with the added benefit of increased safety (sedation vs. GA; no need for laparoscopy), reduced waiting time, and reduced costs (no need for hospital resources or an anesthetist).
Vol. 104, No. 3, Supplement, September 2015