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Down regulation of biomarkers and increased pregnancy rate following GNRH agonist treatment in patients with endometriosis
P-167 Tuesday, October 20, 2015 DOES THE RECURRENCE OF OVARIAN ENDOMETRIOMA AFFECT THE PREGNANCY RATES IN IVF?. K. Aslan,a I. Kasapoglu,b B. Avci,c B. Ata,d G. Uncu.e aUludag University School of Medicine Depart, Gynecology, Bursa, Turkey; bObstetrics and Gynecology, Uludag University School of Medicine, Bursa, Turkey; cHistology/ Embryology, Uludag University Faculty of Medicine, Bursa, Turkey; dRe_ productive Endocrinology and Infertility, Istanbul, Turkey; eUludag University, Bursa, Turkey.
P-166 Tuesday, October 20, 2015 DOWN REGULATION OF BIOMARKERS AND INCREASED PREGNANCY RATE FOLLOWING GNRH AGONIST TREATMENT IN PATIENTS WITH ENDOMETRIOSIS. E. Rahmawati,a P. K. Maurya,b A. Kao,c H. Chen,d C. Tzeng.e aClinical Medicine, Taipei Medical University, Taipei, Taiwan; bAmity Institute of Biotechnology, Amity University, Uttar Pradesh, India; cObstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan; dGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; eTaipei Medical University, Taipei, Taiwan. OBJECTIVE: The present study was undertaken to evaluate the effect of GnRHa in endometriosis patients undergoing IVF. We further investigated the effect of GnRHa on the genes expression and proteins level in endometriotic tissues. We hypothesized that some protein related with pathogenesis of endometriosis are down regulated in the patients following GnRHa treatment. DESIGN: Retrospective case control clinical study combined with analysis of gene expression profile and the protein level in patients with endometriosis after GnRHa treatment. MATERIALS AND METHODS: This study recruited 282 endometriosis women without GnRHa treatment and 96 endometriosis patients with GnRHa treatment. IVF outcome was measured by evaluation on oocyte number, embryo transfer, pregnancy rate, implantation rate and abortion rate. Biopsy of endometriotic tissues was done to evaluate distinction of genes expression with and without GnRHa treatment using affymetrix microarray and independently validated by q-RT PCR, western blot and IHC. The candidate biomarkers from serum were measured by ELISA. Primary culture of endometriotic stroma cells to identify the role of estrogen in the expression of candidate proteins. Statistical analysis was performed using Mann-Whitney U test. P < 0.05 is considered significant. RESULTS: IVF outcome shown that implantation rate increased significantly in endometriosis patients with GnRHa treatment (25.4%) compared with untreated group (18.7%) (p¼0.001) and the pregnancy rate increased significantly in treated patient (39.3%) compared with untreated group (19.7%) (p¼0.003). This data was Supported by microarray data that approximately 65 genes exhibited alterations in expression following GnRHa treatment. Validation using q-RT PCR, WB, IHC and ELISA indicated that TNS1, MMP 14, CAV 2, NRN1 and ATP2A3 were significantly lower in patients with GnRHa treatment. P values are in the following manner: Tensin 1 (p¼ 0.0100), MMP 14 (p¼ 0.013), Caveolin 2 (p¼ 0.023), Neuritin 1 (p¼ 0.040) and ATP2A3 (p¼ 0.044). Immunohostochemistry indicated that stromal cells expressed the five candidates proteins. Treatment with estradiol on stroma endometriotic cells increased the expression of those proteins. Tensin 1 and MMP 14 play important role in cell migration. The role of Caveolin 2 is poorly understood. Neuritin 1 is associated with pain. ATP2A3 is involved in calcium sequestration associated with muscular excitation and contraction. CONCLUSIONS: GnRHa treatment in endometriosis patients increased implantation and pregnancy rate in women undergoing IVF and down regulated the promising prognostic biomarkers: Tensin 1, MMP 14, Caveolin 2, Neuritin 1 and ATP2A3. Supported by: This work was Supported by the funding from the Academia Sinica (BM104010117) and MOST(103-2314-B-038-054-MY2) of Taiwan
FERTILITY & STERILITYÒ
OBJECTIVE: To determine whether recurrence of endometrioma affects ongoing pregnancy rates in IVF cycles. DESIGN: Retrospective Study MATERIALS AND METHODS: This is a retrospective study conducted at Uludag University Faculty of Medicine, Department of Obstetrics and Gynecology. Electronic data of the years between 2011-2015 was screened and IVF patients with endometriosis were selected. Patiens were classified into three subgroups; patients with recurrence of endometrioma (Group 1), patients with primary endometrioma (Group-2) and patients without recurrence of endometrioma after surgery(Group-3) . Baseline characteristics, embroloygy laboratory parameters and pregnancy outcomes were analyzed and compared. RESULTS: Total 62 infertile patients with endometriosis were selected from electronic database. Baseline characteristics were similar in each group. Median duration after surgery was 2 years for IVF. 24 of these 42 patients with surgical history have had postoperative recurrence of endometrioma during ovarian stimulation. There have been 42 patients with endometrioma during ovarian stimulation. Mean endometrioma size was 3,48 cm (+/- 2,1). 24 of 42 patients had recurrence of endometrioma and 18 of 42 patients had primary endometrioma. The rest of 62 patients had been surgery before and there were no recurrence of endometrioma in these patients. Embryologic laboratory parameters and ongoing pregnancy rates (OPR) were similar in three groups. Number of picked up oocytes were 7,8 (+/-4,8), 12,3(+/-8,7) and 10,2(+/-6,6), p:0,258, respectively group 1,2,3. Number of metaphase2 oocytes were 5,6(+/-3,7), 7,89(+/-5,1) and 7,9(+/-6,1), p:0.164, respectively group 1,2,3. Pregnancy outcomes were analyzed in two parameters; positive B-hCG and ongoing pregnancy rate. Positive B-hCG rates were % 58.3, %33.3, %55, respectively group 1,2,3, p:0.244. Ongoing pregnancy rates were %33.3, %22.2, %35, respectively group 1,2,3, p:0.655. CONCLUSIONS: Presence of endometrioma during ovarian stimulation in infertile patients does not affect embryology laboratory parameters and pregnancy outcomes. After surgical removal, presence of recurrence does not decrease pregnancy outcomes. Thus in conclusion, there is no need to re-operate the patients for removal of recurrence for better IVF outcomes. Embryology and Pregnancy Outcomes. Group 3 Group 2 Group 1 Surgery (+) Surgery (-) Surgery (+) Endometrioma (+) Endometrioma (+) Endometrioma (-) p value Number of oocyte (sd) Number of metaphase 2 oocyte (sd) Number of 2PN (sd) Positive b-hCG (%) Ongoing Pregnancy Rate (%)
7,8 (+/-4,8) 5,6(+/-3,7)
12,3(+/-8,7) 7,89(+/-5,1)
10,2(+/-6,6) 7,9(+/-6,1)
0,164 0.258
4,17(+/-2,8) 14/24 (%58.3) 8/24 (%33.3)
5,4(+/-4) 6/18 (%33.3) 4/18 (%22.2)
5,2(+/-3,9) 11/20 (%55) 7/20 (%35)
0.518 0.244 0.655
P-168 Tuesday, October 20, 2015 IMPROVEMENT IN ENDOMETRIOSIS-RELATED PELVIC PAIN WITH LEUPROLIDE OR NORETHINDRONE TREATMENT. O. Muneyyirci-Delale,a,b C. Charles,a N. Sinaii,c M. Dalloul,a d a P. Stratton. OB/GYN, SUNY Downstate Medical Center, Brooklyn, NY; b Ob/gyn, Kings County Hospital Center, Brooklyn, MD; cNational Institutes of Health, Bethesda, MD; dNICHD, NIH, Bethesda, MD. OBJECTIVE: To compare the long-term effectiveness of 24 weeks Leuprolide Acetate Depot form 11.25mg (LD) vs Norethindrone Acetate 5mg (NA) followed by NA alone for 28 weeks in relieving pain from endometriosis. DESIGN: Prospective double-masked randomized clinical trial
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P-166 Tuesday, October 20, 2015 DOWN REGULATION OF BIOMARKERS AND INCREASED PREGNANCY RATE FOLLOWING GNRH AGONIST TREATMENT IN PATIENTS WITH ENDOMETRIOSIS. E. Rahmawati,a P. K. Maurya,b A. Kao,c H. Chen,d C. Tzeng.e aClinical Medicine, Taipei Medical University, Taipei, Taiwan; bAmity Institute of Biotechnology, Amity University, Uttar Pradesh, India; cObstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan; dGraduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; eTaipei Medical University, Taipei, Taiwan. OBJECTIVE: The present study was undertaken to evaluate the effect of GnRHa in endometriosis patients undergoing IVF. We further investigated the effect of GnRHa on the genes expression and proteins level in endometriotic tissues. We hypothesized that some protein related with pathogenesis of endometriosis are down regulated in the patients following GnRHa treatment. DESIGN: Retrospective case control clinical study combined with analysis of gene expression profile and the protein level in patients with endometriosis after GnRHa treatment. MATERIALS AND METHODS: This study recruited 282 endometriosis women without GnRHa treatment and 96 endometriosis patients with GnRHa treatment. IVF outcome was measured by evaluation on oocyte number, embryo transfer, pregnancy rate, implantation rate and abortion rate. Biopsy of endometriotic tissues was done to evaluate distinction of genes expression with and without GnRHa treatment using affymetrix microarray and independently validated by q-RT PCR, western blot and IHC. The candidate biomarkers from serum were measured by ELISA. Primary culture of endometriotic stroma cells to identify the role of estrogen in the expression of candidate proteins. Statistical analysis was performed using Mann-Whitney U test. P < 0.05 is considered significant. RESULTS: IVF outcome shown that implantation rate increased significantly in endometriosis patients with GnRHa treatment (25.4%) compared with untreated group (18.7%) (p¼0.001) and the pregnancy rate increased significantly in treated patient (39.3%) compared with untreated group (19.7%) (p¼0.003). This data was Supported by microarray data that approximately 65 genes exhibited alterations in expression following GnRHa treatment. Validation using q-RT PCR, WB, IHC and ELISA indicated that TNS1, MMP 14, CAV 2, NRN1 and ATP2A3 were significantly lower in patients with GnRHa treatment. P values are in the following manner: Tensin 1 (p¼ 0.0100), MMP 14 (p¼ 0.013), Caveolin 2 (p¼ 0.023), Neuritin 1 (p¼ 0.040) and ATP2A3 (p¼ 0.044). Immunohostochemistry indicated that stromal cells expressed the five candidates proteins. Treatment with estradiol on stroma endometriotic cells increased the expression of those proteins. Tensin 1 and MMP 14 play important role in cell migration. The role of Caveolin 2 is poorly understood. Neuritin 1 is associated with pain. ATP2A3 is involved in calcium sequestration associated with muscular excitation and contraction. CONCLUSIONS: GnRHa treatment in endometriosis patients increased implantation and pregnancy rate in women undergoing IVF and down regulated the promising prognostic biomarkers: Tensin 1, MMP 14, Caveolin 2, Neuritin 1 and ATP2A3. Supported by: This work was Supported by the funding from the Academia Sinica (BM104010117) and MOST(103-2314-B-038-054-MY2) of Taiwan
FERTILITY & STERILITYÒ
OBJECTIVE: To determine whether recurrence of endometrioma affects ongoing pregnancy rates in IVF cycles. DESIGN: Retrospective Study MATERIALS AND METHODS: This is a retrospective study conducted at Uludag University Faculty of Medicine, Department of Obstetrics and Gynecology. Electronic data of the years between 2011-2015 was screened and IVF patients with endometriosis were selected. Patiens were classified into three subgroups; patients with recurrence of endometrioma (Group 1), patients with primary endometrioma (Group-2) and patients without recurrence of endometrioma after surgery(Group-3) . Baseline characteristics, embroloygy laboratory parameters and pregnancy outcomes were analyzed and compared. RESULTS: Total 62 infertile patients with endometriosis were selected from electronic database. Baseline characteristics were similar in each group. Median duration after surgery was 2 years for IVF. 24 of these 42 patients with surgical history have had postoperative recurrence of endometrioma during ovarian stimulation. There have been 42 patients with endometrioma during ovarian stimulation. Mean endometrioma size was 3,48 cm (+/- 2,1). 24 of 42 patients had recurrence of endometrioma and 18 of 42 patients had primary endometrioma. The rest of 62 patients had been surgery before and there were no recurrence of endometrioma in these patients. Embryologic laboratory parameters and ongoing pregnancy rates (OPR) were similar in three groups. Number of picked up oocytes were 7,8 (+/-4,8), 12,3(+/-8,7) and 10,2(+/-6,6), p:0,258, respectively group 1,2,3. Number of metaphase2 oocytes were 5,6(+/-3,7), 7,89(+/-5,1) and 7,9(+/-6,1), p:0.164, respectively group 1,2,3. Pregnancy outcomes were analyzed in two parameters; positive B-hCG and ongoing pregnancy rate. Positive B-hCG rates were % 58.3, %33.3, %55, respectively group 1,2,3, p:0.244. Ongoing pregnancy rates were %33.3, %22.2, %35, respectively group 1,2,3, p:0.655. CONCLUSIONS: Presence of endometrioma during ovarian stimulation in infertile patients does not affect embryology laboratory parameters and pregnancy outcomes. After surgical removal, presence of recurrence does not decrease pregnancy outcomes. Thus in conclusion, there is no need to re-operate the patients for removal of recurrence for better IVF outcomes. Embryology and Pregnancy Outcomes. Group 3 Group 2 Group 1 Surgery (+) Surgery (-) Surgery (+) Endometrioma (+) Endometrioma (+) Endometrioma (-) p value Number of oocyte (sd) Number of metaphase 2 oocyte (sd) Number of 2PN (sd) Positive b-hCG (%) Ongoing Pregnancy Rate (%)
7,8 (+/-4,8) 5,6(+/-3,7)
12,3(+/-8,7) 7,89(+/-5,1)
10,2(+/-6,6) 7,9(+/-6,1)
0,164 0.258
4,17(+/-2,8) 14/24 (%58.3) 8/24 (%33.3)
5,4(+/-4) 6/18 (%33.3) 4/18 (%22.2)
5,2(+/-3,9) 11/20 (%55) 7/20 (%35)
0.518 0.244 0.655
P-168 Tuesday, October 20, 2015 IMPROVEMENT IN ENDOMETRIOSIS-RELATED PELVIC PAIN WITH LEUPROLIDE OR NORETHINDRONE TREATMENT. O. Muneyyirci-Delale,a,b C. Charles,a N. Sinaii,c M. Dalloul,a d a P. Stratton. OB/GYN, SUNY Downstate Medical Center, Brooklyn, NY; b Ob/gyn, Kings County Hospital Center, Brooklyn, MD; cNational Institutes of Health, Bethesda, MD; dNICHD, NIH, Bethesda, MD. OBJECTIVE: To compare the long-term effectiveness of 24 weeks Leuprolide Acetate Depot form 11.25mg (LD) vs Norethindrone Acetate 5mg (NA) followed by NA alone for 28 weeks in relieving pain from endometriosis. DESIGN: Prospective double-masked randomized clinical trial
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