- Email: [email protected]
Balanced LYCAT gene expression is crucial for female reproduction
endometrial biopsies, and the ICSI outcomes for patients presenting or not recurrent implantation failure (RIF). DESIGN: Cohort study. MATERIALS AND METHODS: This study included 211 patients submitted to infertility screening at a private reproductive medicine center. All patients underwent office hysteroscopy followed by endometrial biopsy, and received prophylactic antibiotic therapy with vibramycin. 105 patients were submitted to ICSI cycle. The ovarian stimulation protocol used GnRH-agonist or antagonist, recombinant-FSH (Gonal-F, Serono), and recombinant-hCG (Ovidrel, Serono). ICSI outcomes were evaluated according to groups: patients without previous IVF (FIRST-IVF: n ¼ 36), RIF patients defined as at least 3 previous unsuccessful IVF (RIF: n ¼ 18), and patients who underwent previous low complexity or 1-2 IVF cycles (INTER: n ¼ 51). RESULTS: The mean age of patients were similar between groups (FIRST IVF: 34.8 4.6; RIF: 36.5 5.7; INTER: 36.4 4.7; P¼0.280). The number of previous ICSI cycles was 4.1 1.4 for RIF patients and 0.4 0.7 for INTER group. In spite of prevalence of endometrial alteration at hysteroscopy in the RIF group had been higher (66.7%) than FIRST IVF (27.3%; P¼0.006) and INTER (37.0%; P¼0.032) groups, the prevalence of alterations at pathologic analysis was not significant (P¼0.592). After prophylactic antibiotic therapy with vibramycin, patients underwent ICSI cycles (1.5 0.5 cycles per patient), and accumulated ongoing pregnancy rate was 30.6% in FIRST-IVF, 29.4% for RIF and 42.9% in INTER groups (P¼0.411). CONCLUSION: Endometrial alteration at hysteroscopy was higher in the RIF group. After hysteroscopy and prophylactic antibiotic therapy, the accumulated ongoing pregnancy rate was 30% in RIF, which was similar to other groups without RIF. Our results suggest that hysteroscopy and prophylactic antibiotic therapy should be favorable in patients with RIF.
P-571 Wednesday, October 19, 2011 LETROZOLE USE IN FROZEN EMBYRO TRANSFER (FET) CYCLES: CLINICAL PREGNANCY OUTCOMES IN PATIENTS WITH AND WITHOUT ENDOMETRIOSIS. B. G. Patel, G. Bushnell, H. L. Higdon, III, P B. Miller, D. A. Forstein, B. A. Lessey. Obstetrics and Gynecology Division Reproductive Endocrinology and Infertility, Greenville Hospital System, Greenville, SC; Department of Public Health Sciences, Clemson University, Clemson, SC. OBJECTIVE: Aromatase has been associated with poor reproductive outcome during In Vitro Fertilization (IVF) and aromatase inhibitors like letrozole appear to be helpful in poor responders. The purpose of this study was to examine the effectiveness of letrozole, administered during a frozen embryo transfer (FET) cycle in women with and without diagnosed endometriosis. DESIGN: Retrospective case control study on FET cycles between January 2003 and December 2010. MATERIALS AND METHODS: The study population comprised 173 first time FET cycles. Overall, 61 of 173 subjects (35.3%) were diagnosed with endometriosis. Of the 112 patients without a diagnosis of endometriosis 27/112 (24.1%) had a prior laparoscopy. Twenty-two of 173 (12.7%) received letrozole (2.5 to 5 mg on days 3 to 7 of their FET cycle) along with the standard hormone replacement. Of the patients on letrozole, 17/22 (77.3%) had endometriosis. The control group included 105 patients without a diagnosis of endometriosis who received no letrozole. Statistical analyses included the Pearson chi-square test for outcome and demographic variables and the student t-test for continuous demographic variables. RESULTS: Demographics were similar between groups. Of the patients with endometriosis that received letrozole, clinical pregnancy was achieved in 10/17 (58.8%) compared to 30 of 105 (28.6%) in the control group (P¼0.02). None of 5 patients without known endometriosis who received letrozole during their FET cycle conceived. The quality of transfer was examined between groups. When only excellent transfers were included, the clinical pregnancy rate difference (10/15; 66.7% vs. 23/75; 30.3%, respectively), was significantly in favor of letrozole (P¼0.008). CONCLUSION: Letrozole is an effective adjunct therapy for women undergoing FET with a history of endometriosis. These women were more likely to have a clinical pregnancy compared to patients without endometriosis not receiving letrozole during FET, possibly through improvement in endometrial receptivity.
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P-572 Wednesday, October 19, 2011 ABERRANT EXPRESSION OF HOMEOBOX GENES ADVERSELY AFFECTS IMPLANTATION IN ENDOMETRIOSIS. S. K. Jana, P. Banerjee, V. Pramanik, P. Pasricha, K. Chaudhury, B. Chakravarty. School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India; Department of Biotechnology, National Institute of Technology, Durgapur, West Bengal, India; Reproductive Health, Institute of Reproductive Medicine, Kolkata, West Bengal, India. OBJECTIVE: To investigate Homeobox genes HOXA-10 and HOXA-11 mediated endometrial molecular defects during implantation window in endometriosis-associated infertility cases. DESIGN: A prospective comparative study conducted on 31 women with endometriosis (age<35 years) during their mid-secretory phase of the menstrual cycle and 26 age-matched fertile women as controls reporting to the Institute of Reproductive Medicine, India. The effect of endometrial HOXA-10 and HOXA-11 genes on the mediators of matrix turnover, MMP-2 and -9 and on endometrial receptivity markers including avb3 integrin, leukemia inhibitory factor (LIF) and pinopodes were explored in women with endometriosis. MATERIALS AND METHODS: Endometrial tissue samples collected during implantation window from both endometriotic and normal women were divided into four parts: stromal and epithelial cells were isolated from the first part for flow cytometric analysis of avb3 integrin and LIF expression, the second part was fixed to examine pinopodes expression by scanning electron microscopy, and mRNA were isolated from the third part to study HOXA-10 and HOXA-11 gene expression by Real Time PCR. The fourth part was used to study the expression of MMP-2, -9, HOXA-10 and -11 by Western blot. Data were compared by independent two sample ‘t’ test, and chi-square test, as applicable. Statistical significance was defined as P%0.05. RESULTS: A significantly higher endometrial expression of HOXA-11, MMP-2 and -9 were observed in women with endometriosis when compared with controls. Interestingly, expression of HOXA-10 gene was significantly less in endometriosis which is known to regulate the expression of endometrial receptivity markers. CONCLUSION: The findings suggest that aberrant expression of HOXA10 and -11 genes adversely affects endometrial remodeling and expression of receptivity markers. Suitable HOX gene therapy to improve implantation appears to be a promising area of research in the subsequent years. Supported by: Saikat k Jana was supported by a fellowship from ICMR, India.
P-573 Wednesday, October 19, 2011 BALANCED LYCAT GENE EXPRESSION IS CRUCIAL FOR FEMALE REPRODUCTION. L. Ni, W. Wang, Y. Tang, H.-C. Liu. Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY. OBJECTIVE: To test our hypothesis that lysocardiolipin acyltransferase (Lycat) is a key regulator controlling the developmental potential of early embryos and uterine receptivity of the mothers. DESIGN: Experimental study. Transgenic (Tg) mouse lines over-expressing Lycat were generated. Our hypothesis was tested by analyzing the phenotype and the underlying molecular mechanism leading to infertility. MATERIALS AND METHODS: Full length cDNA and ires.lacZ were inserted into the 2nd exon of a Lycat BAC clone by ET-cloning. Tg lines were generated by pronuclear injection. Litter size from intercross breedings of Tg mice was documented. Embryos were collected at different stages to detect the onset of degeneration. Fully expanded WT and Tg blastocysts were placed on slides and fixed with 4% PFA. Cell number was obtained by counting DAPI-stained nuclei. WT, Tg blastocysts as well as endometrial stromal cells (ESCs) were boiled in water for 40 min. to release ATP. Equal volume of rL/L reagent from Promega ENLITEN ATP system was added. RLU was measured with GloMax20/20. RESULTS: Lycat is a cardiolipin remodeling enzyme. Elevate level of cardiolipin antibodies in humans results in impaired implantation. The female Tg mice exhibit reduced fertility as they either produce fewer pups per litter (Wt, 8.3 1.2; n ¼ 16. vs Tg, 3.6 1.6, n ¼ 32; P<0.01), or are infertile. Degeneration of Tg embryos started at implantation stage (E4.5) and completed by E11.5. Tg blastocysts contain fewer cells than the WTs (Tg, 69.5 6.4,n ¼ 6. vs.WT, 81.5 4.2, n ¼ 6; P<0.05). ATP assay shows that
Vol. 96., No. 3, Supplement, September 2011
a single WT blastocyst has an average ATP content of 0.23 0.01 picomoles; whereas Tg blastocysts show a 47% reduction to 0.13 0.02 picomoles (P<0.01) of ATP. Furthermore, a 17% decrease in ATP level was detected in the Tg ESCs as compared to WTs (Wt, 1.35 0.15 vs. Tg, 1.13 0.10; P<0.05). CONCLUSION: Decrease in ATP levels of blastocysts and uterine ESCs by excess Lycat demonstrates that Lycat regulates the metabolic rate of both embryos and adult female reproductive tracts.
P-574 Wednesday, October 19, 2011 ENDOMETRIAL INJURY MAY INCREASE THE CLINICAL PREGNANCY RATE IN NORMORESPONDERS UNDERWENT LONG AGONIST PROTOCOL INTRACYTOPLASMIC SPERM INJECTION CYCLES WITH SINGLE EMBRYO TRANSFER. S. Guven, C. Kart, M. A. Unsal, O. Yildirim, E. Odaci, E. Yulug. Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey. OBJECTIVE: To investigate the effect of endometrial injury on clinical pregnancy rate in normoresponder patients undergoing long agonist protocol intracytoplasmic sperm injection cycles with single embryo transfer. DESIGN: Prospective case control study. MATERIALS AND METHODS: One hundred-thirty women were included. All patients had following criteria; age under 35, normoresponder, and having grade I or II embryos for transfer. All patients were stimulated with luteal phase long protocol. Leuprolide acetate (Lucrin, Abbot, Istanbul, Turkey) was started at the luteal phase. Recombinant-FSH (Gonal F, Serono, Istanbul, Turkey) was administered in a step-down protocol and starting with a 225 IU/day after step down regulation confirmation. Recombinant human chorionic gonadotropin (Ovitrelle 0.25 mgr IM, Serono, Istanbul, Turkey) was administered when at least two or three follicles reached a mean diameter of 17 mm. Oocyte retrieval was performed 36 h later than HCG, ICSI was performed for all patients and day 3 embryo transfer was preferred. All patients had single embryo transfer. Patients of the study group (n ¼ 56, group I) were randomly selected to undergo endometrial biopsy on day 3 of menstrual cycle following down regulation. Patients of the control group (n ¼ 62, group II) were not underwent endometrial biopsy procedure. Clinical pregnancy was defined as presence of a gestational sac with accompanying fetal heart beat under ultrasound 4 weeks after embryo transfer. Fisher exact chi-square test was used for statistical analysis. RESULTS: The clinical and embryologic characteristics were comparable in two groups. The clinical pregnancy rate was 48.2% in group I while this rate was 29.0% in group II (P¼0.025, Fisher exact chi-square test). CONCLUSION: This study suggests that assisted reproduction technology treatment that is preceded by endometrial biopsy may increase the pregnancy rates in women undergoing luteal long agonist protocol intracytoplasmic sperm injection cycles with single embryo transfer.
P-575 Wednesday, October 19, 2011 € PATIENTS WITH MULLERIAN ANOMALIES HAVE LOWER EMBRYO IMPLANTATION IN OOCYTE DONATION. S. Portela, I. Fernandez, T. Lopez, B. Martinez, J. Aguilar, E. Munoz. Reproductive Medicine, IVI Vigo, Vigo, Pontevedra, Spain. OBJECTIVE: Our aim was to evaluate the reproductive outcome of women with M€ ullerian anomalies (MA) treated with oocyte donation (OD) and compare them with receptors of oocytes with idiopathic premature ovarian failure (POF). DESIGN: A comparative retrospective study. MATERIALS AND METHODS: 66 patients with MA who underwent 70 cycles of OD were retrospectively compared with the next following file in our OD program with idiopathic POF (n ¼ 70) between January 2000 and July 2010. Idiopathic POF was defined as POF with normal karyotype, absence of autoimmune endocrine disease, absence of ovarian surgery and absence of premutations for X fragile syndrome. We studied 33
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patients with bicornuate uteri, 21 patients with septate uteri, 9 patients with unicornuate uteri and 3 patients with didelphis uteri. The main outcome measures were pregnancy, implantation, miscarriage and ongoing pregnancy rates. For statistical analysis, a P<0.05 was considered to indicate significance. RESULTS: No differences were found among the recipients for age, duration or uterine preparation, mean number of oocytes donated, fertilization rates, and mean number of embryos transferred. Male factor was also similar between groups. Among their donors, no significant difference was noted for mean age, or parameters of ovarian stimulation. There was detectable difference in pregnancy rates between the group of patients with MA (40.7%) and idiopathic POF (69.6%)(P¼0.023). Implantation rates were 30.5 % and 47.3%, respectively, also differents (P¼0.021). Miscarriage rates were 20.0% in patients with MA and 11.4% in idiopathic POF and ongoing pregnancy rate were 20.7% and 56.8% also with significant differences. Ectopic pregnancy rate was similar between groups (MA: 0% and POF: 1,4%)(P¼0.368). CONCLUSION: Patients with M€ullerian anomalies have lower pregnancy and implantation rates and higher miscarriage rate than patients with idiopathic POF. This issue should be explored in more studies to confirm our findings.
P-576 Wednesday, October 19, 2011 ENDOMETRIAL INJURY AND OUTCOME OF THE SUBSEQUENT IVF CYCLE. A SYSTEMATIC REVIEW AND METAANALYSIS. T. A. El-Toukhy, S. K. Sunkara, Y. Khalaf. Assisted Conception Unit, Guy’s and St. Thomas’ Hospital, London, United Kingdom. OBJECTIVE: We sought to examine whether inducing endometrial injury before starting an IVF cycle could improve the implantation rate after embryo transfer. DESIGN: Systematic review of published literature MATERIALS AND METHODS: We conducted a systematic review of literature to evaluate the impact of endometrial injury on the outcome of the subsequent IVF cycle. MEDLINE, EMBASE, the Cochrane Library, ISI Conference Proceedings and ISRCTN Register were searched for published studies up to April 2011. We included studies comparing outcome of IVF treatment in patients who had endometrial injury in the cycle preceding their IVF treatment with a control group in which endometrial injury was not performed. Study selection and data extraction were performed in duplicate. Main outcome measures were clinical pregnancy (CPR) and live birth (LBR) rates in the subsequent IVF cycle. RESULTS: In total, 647 participants in 6 studies were included: 2 randomized (n ¼ 204) and 4 non-randomized controlled studies (n ¼ 443). The quality of the studies was variable. All 6 studies showed improvement in treatment outcome after endometrial injury compared to the control group with no statistical heterogeneity. Meta-analyses of the results of these studies showed benefit from endometrial injury prior to IVF treatment in improving the CPR (pooled relative risk (RR) ¼ 2.4, 95% CI 1.9-3.1, P¼0.0001) and the LBR (RR ¼ 2.3, 95% CI 1.7-3.1, P¼0.0001) in the subsequent IVF cycle. Evidence from the 2 randomized trials was consistent with that from the 4 non-randomized controlled studies. Sensitivity analysis of the 4 studies which only included recurrent implantation failure patients (n ¼ 455) showed improved CPR (RR ¼ 2.4, 95% CI 1.8-3.3, P¼0.001) and LBR (RR ¼ 2.2, 95% CI 1.5-3.3, P¼0.001) in the intervention group. CONCLUSION: Endometrial injury improves the outcome of the subsequent IVF treatment cycle. Large and robust randomized trials comparing endometrial injury with no intervention before IVF treatment are needed to further guide clinical practice.
P-577 Wednesday, October 19, 2011 ENDOMETRIAL INJURY VIA SALINE-INFUSION SONOHYSTEROGRAM (SIS) PERFORMED WITHIN ONE MONTH OF CYCLE START DOES NOT IMPROVE LIVE BIRTH RATE. M. C. Peavey, A. A. Shah, D. J. Raburn, D. K. Walmer, S. D. Copland, T. M. Price. Duke Fertility Center, Duke University Medical Center, Durham, NC. OBJECTIVE: Approximately two-thirds of implantation failures following in vitro fertilization (IVF) are due to inadequate uterine receptivity.
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P-571 Wednesday, October 19, 2011 LETROZOLE USE IN FROZEN EMBYRO TRANSFER (FET) CYCLES: CLINICAL PREGNANCY OUTCOMES IN PATIENTS WITH AND WITHOUT ENDOMETRIOSIS. B. G. Patel, G. Bushnell, H. L. Higdon, III, P B. Miller, D. A. Forstein, B. A. Lessey. Obstetrics and Gynecology Division Reproductive Endocrinology and Infertility, Greenville Hospital System, Greenville, SC; Department of Public Health Sciences, Clemson University, Clemson, SC. OBJECTIVE: Aromatase has been associated with poor reproductive outcome during In Vitro Fertilization (IVF) and aromatase inhibitors like letrozole appear to be helpful in poor responders. The purpose of this study was to examine the effectiveness of letrozole, administered during a frozen embryo transfer (FET) cycle in women with and without diagnosed endometriosis. DESIGN: Retrospective case control study on FET cycles between January 2003 and December 2010. MATERIALS AND METHODS: The study population comprised 173 first time FET cycles. Overall, 61 of 173 subjects (35.3%) were diagnosed with endometriosis. Of the 112 patients without a diagnosis of endometriosis 27/112 (24.1%) had a prior laparoscopy. Twenty-two of 173 (12.7%) received letrozole (2.5 to 5 mg on days 3 to 7 of their FET cycle) along with the standard hormone replacement. Of the patients on letrozole, 17/22 (77.3%) had endometriosis. The control group included 105 patients without a diagnosis of endometriosis who received no letrozole. Statistical analyses included the Pearson chi-square test for outcome and demographic variables and the student t-test for continuous demographic variables. RESULTS: Demographics were similar between groups. Of the patients with endometriosis that received letrozole, clinical pregnancy was achieved in 10/17 (58.8%) compared to 30 of 105 (28.6%) in the control group (P¼0.02). None of 5 patients without known endometriosis who received letrozole during their FET cycle conceived. The quality of transfer was examined between groups. When only excellent transfers were included, the clinical pregnancy rate difference (10/15; 66.7% vs. 23/75; 30.3%, respectively), was significantly in favor of letrozole (P¼0.008). CONCLUSION: Letrozole is an effective adjunct therapy for women undergoing FET with a history of endometriosis. These women were more likely to have a clinical pregnancy compared to patients without endometriosis not receiving letrozole during FET, possibly through improvement in endometrial receptivity.
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P-572 Wednesday, October 19, 2011 ABERRANT EXPRESSION OF HOMEOBOX GENES ADVERSELY AFFECTS IMPLANTATION IN ENDOMETRIOSIS. S. K. Jana, P. Banerjee, V. Pramanik, P. Pasricha, K. Chaudhury, B. Chakravarty. School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India; Department of Biotechnology, National Institute of Technology, Durgapur, West Bengal, India; Reproductive Health, Institute of Reproductive Medicine, Kolkata, West Bengal, India. OBJECTIVE: To investigate Homeobox genes HOXA-10 and HOXA-11 mediated endometrial molecular defects during implantation window in endometriosis-associated infertility cases. DESIGN: A prospective comparative study conducted on 31 women with endometriosis (age<35 years) during their mid-secretory phase of the menstrual cycle and 26 age-matched fertile women as controls reporting to the Institute of Reproductive Medicine, India. The effect of endometrial HOXA-10 and HOXA-11 genes on the mediators of matrix turnover, MMP-2 and -9 and on endometrial receptivity markers including avb3 integrin, leukemia inhibitory factor (LIF) and pinopodes were explored in women with endometriosis. MATERIALS AND METHODS: Endometrial tissue samples collected during implantation window from both endometriotic and normal women were divided into four parts: stromal and epithelial cells were isolated from the first part for flow cytometric analysis of avb3 integrin and LIF expression, the second part was fixed to examine pinopodes expression by scanning electron microscopy, and mRNA were isolated from the third part to study HOXA-10 and HOXA-11 gene expression by Real Time PCR. The fourth part was used to study the expression of MMP-2, -9, HOXA-10 and -11 by Western blot. Data were compared by independent two sample ‘t’ test, and chi-square test, as applicable. Statistical significance was defined as P%0.05. RESULTS: A significantly higher endometrial expression of HOXA-11, MMP-2 and -9 were observed in women with endometriosis when compared with controls. Interestingly, expression of HOXA-10 gene was significantly less in endometriosis which is known to regulate the expression of endometrial receptivity markers. CONCLUSION: The findings suggest that aberrant expression of HOXA10 and -11 genes adversely affects endometrial remodeling and expression of receptivity markers. Suitable HOX gene therapy to improve implantation appears to be a promising area of research in the subsequent years. Supported by: Saikat k Jana was supported by a fellowship from ICMR, India.
P-573 Wednesday, October 19, 2011 BALANCED LYCAT GENE EXPRESSION IS CRUCIAL FOR FEMALE REPRODUCTION. L. Ni, W. Wang, Y. Tang, H.-C. Liu. Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY. OBJECTIVE: To test our hypothesis that lysocardiolipin acyltransferase (Lycat) is a key regulator controlling the developmental potential of early embryos and uterine receptivity of the mothers. DESIGN: Experimental study. Transgenic (Tg) mouse lines over-expressing Lycat were generated. Our hypothesis was tested by analyzing the phenotype and the underlying molecular mechanism leading to infertility. MATERIALS AND METHODS: Full length cDNA and ires.lacZ were inserted into the 2nd exon of a Lycat BAC clone by ET-cloning. Tg lines were generated by pronuclear injection. Litter size from intercross breedings of Tg mice was documented. Embryos were collected at different stages to detect the onset of degeneration. Fully expanded WT and Tg blastocysts were placed on slides and fixed with 4% PFA. Cell number was obtained by counting DAPI-stained nuclei. WT, Tg blastocysts as well as endometrial stromal cells (ESCs) were boiled in water for 40 min. to release ATP. Equal volume of rL/L reagent from Promega ENLITEN ATP system was added. RLU was measured with GloMax20/20. RESULTS: Lycat is a cardiolipin remodeling enzyme. Elevate level of cardiolipin antibodies in humans results in impaired implantation. The female Tg mice exhibit reduced fertility as they either produce fewer pups per litter (Wt, 8.3 1.2; n ¼ 16. vs Tg, 3.6 1.6, n ¼ 32; P<0.01), or are infertile. Degeneration of Tg embryos started at implantation stage (E4.5) and completed by E11.5. Tg blastocysts contain fewer cells than the WTs (Tg, 69.5 6.4,n ¼ 6. vs.WT, 81.5 4.2, n ¼ 6; P<0.05). ATP assay shows that
Vol. 96., No. 3, Supplement, September 2011
a single WT blastocyst has an average ATP content of 0.23 0.01 picomoles; whereas Tg blastocysts show a 47% reduction to 0.13 0.02 picomoles (P<0.01) of ATP. Furthermore, a 17% decrease in ATP level was detected in the Tg ESCs as compared to WTs (Wt, 1.35 0.15 vs. Tg, 1.13 0.10; P<0.05). CONCLUSION: Decrease in ATP levels of blastocysts and uterine ESCs by excess Lycat demonstrates that Lycat regulates the metabolic rate of both embryos and adult female reproductive tracts.
P-574 Wednesday, October 19, 2011 ENDOMETRIAL INJURY MAY INCREASE THE CLINICAL PREGNANCY RATE IN NORMORESPONDERS UNDERWENT LONG AGONIST PROTOCOL INTRACYTOPLASMIC SPERM INJECTION CYCLES WITH SINGLE EMBRYO TRANSFER. S. Guven, C. Kart, M. A. Unsal, O. Yildirim, E. Odaci, E. Yulug. Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey. OBJECTIVE: To investigate the effect of endometrial injury on clinical pregnancy rate in normoresponder patients undergoing long agonist protocol intracytoplasmic sperm injection cycles with single embryo transfer. DESIGN: Prospective case control study. MATERIALS AND METHODS: One hundred-thirty women were included. All patients had following criteria; age under 35, normoresponder, and having grade I or II embryos for transfer. All patients were stimulated with luteal phase long protocol. Leuprolide acetate (Lucrin, Abbot, Istanbul, Turkey) was started at the luteal phase. Recombinant-FSH (Gonal F, Serono, Istanbul, Turkey) was administered in a step-down protocol and starting with a 225 IU/day after step down regulation confirmation. Recombinant human chorionic gonadotropin (Ovitrelle 0.25 mgr IM, Serono, Istanbul, Turkey) was administered when at least two or three follicles reached a mean diameter of 17 mm. Oocyte retrieval was performed 36 h later than HCG, ICSI was performed for all patients and day 3 embryo transfer was preferred. All patients had single embryo transfer. Patients of the study group (n ¼ 56, group I) were randomly selected to undergo endometrial biopsy on day 3 of menstrual cycle following down regulation. Patients of the control group (n ¼ 62, group II) were not underwent endometrial biopsy procedure. Clinical pregnancy was defined as presence of a gestational sac with accompanying fetal heart beat under ultrasound 4 weeks after embryo transfer. Fisher exact chi-square test was used for statistical analysis. RESULTS: The clinical and embryologic characteristics were comparable in two groups. The clinical pregnancy rate was 48.2% in group I while this rate was 29.0% in group II (P¼0.025, Fisher exact chi-square test). CONCLUSION: This study suggests that assisted reproduction technology treatment that is preceded by endometrial biopsy may increase the pregnancy rates in women undergoing luteal long agonist protocol intracytoplasmic sperm injection cycles with single embryo transfer.
P-575 Wednesday, October 19, 2011 € PATIENTS WITH MULLERIAN ANOMALIES HAVE LOWER EMBRYO IMPLANTATION IN OOCYTE DONATION. S. Portela, I. Fernandez, T. Lopez, B. Martinez, J. Aguilar, E. Munoz. Reproductive Medicine, IVI Vigo, Vigo, Pontevedra, Spain. OBJECTIVE: Our aim was to evaluate the reproductive outcome of women with M€ ullerian anomalies (MA) treated with oocyte donation (OD) and compare them with receptors of oocytes with idiopathic premature ovarian failure (POF). DESIGN: A comparative retrospective study. MATERIALS AND METHODS: 66 patients with MA who underwent 70 cycles of OD were retrospectively compared with the next following file in our OD program with idiopathic POF (n ¼ 70) between January 2000 and July 2010. Idiopathic POF was defined as POF with normal karyotype, absence of autoimmune endocrine disease, absence of ovarian surgery and absence of premutations for X fragile syndrome. We studied 33
FERTILITY & STERILITYÒ
patients with bicornuate uteri, 21 patients with septate uteri, 9 patients with unicornuate uteri and 3 patients with didelphis uteri. The main outcome measures were pregnancy, implantation, miscarriage and ongoing pregnancy rates. For statistical analysis, a P<0.05 was considered to indicate significance. RESULTS: No differences were found among the recipients for age, duration or uterine preparation, mean number of oocytes donated, fertilization rates, and mean number of embryos transferred. Male factor was also similar between groups. Among their donors, no significant difference was noted for mean age, or parameters of ovarian stimulation. There was detectable difference in pregnancy rates between the group of patients with MA (40.7%) and idiopathic POF (69.6%)(P¼0.023). Implantation rates were 30.5 % and 47.3%, respectively, also differents (P¼0.021). Miscarriage rates were 20.0% in patients with MA and 11.4% in idiopathic POF and ongoing pregnancy rate were 20.7% and 56.8% also with significant differences. Ectopic pregnancy rate was similar between groups (MA: 0% and POF: 1,4%)(P¼0.368). CONCLUSION: Patients with M€ullerian anomalies have lower pregnancy and implantation rates and higher miscarriage rate than patients with idiopathic POF. This issue should be explored in more studies to confirm our findings.
P-576 Wednesday, October 19, 2011 ENDOMETRIAL INJURY AND OUTCOME OF THE SUBSEQUENT IVF CYCLE. A SYSTEMATIC REVIEW AND METAANALYSIS. T. A. El-Toukhy, S. K. Sunkara, Y. Khalaf. Assisted Conception Unit, Guy’s and St. Thomas’ Hospital, London, United Kingdom. OBJECTIVE: We sought to examine whether inducing endometrial injury before starting an IVF cycle could improve the implantation rate after embryo transfer. DESIGN: Systematic review of published literature MATERIALS AND METHODS: We conducted a systematic review of literature to evaluate the impact of endometrial injury on the outcome of the subsequent IVF cycle. MEDLINE, EMBASE, the Cochrane Library, ISI Conference Proceedings and ISRCTN Register were searched for published studies up to April 2011. We included studies comparing outcome of IVF treatment in patients who had endometrial injury in the cycle preceding their IVF treatment with a control group in which endometrial injury was not performed. Study selection and data extraction were performed in duplicate. Main outcome measures were clinical pregnancy (CPR) and live birth (LBR) rates in the subsequent IVF cycle. RESULTS: In total, 647 participants in 6 studies were included: 2 randomized (n ¼ 204) and 4 non-randomized controlled studies (n ¼ 443). The quality of the studies was variable. All 6 studies showed improvement in treatment outcome after endometrial injury compared to the control group with no statistical heterogeneity. Meta-analyses of the results of these studies showed benefit from endometrial injury prior to IVF treatment in improving the CPR (pooled relative risk (RR) ¼ 2.4, 95% CI 1.9-3.1, P¼0.0001) and the LBR (RR ¼ 2.3, 95% CI 1.7-3.1, P¼0.0001) in the subsequent IVF cycle. Evidence from the 2 randomized trials was consistent with that from the 4 non-randomized controlled studies. Sensitivity analysis of the 4 studies which only included recurrent implantation failure patients (n ¼ 455) showed improved CPR (RR ¼ 2.4, 95% CI 1.8-3.3, P¼0.001) and LBR (RR ¼ 2.2, 95% CI 1.5-3.3, P¼0.001) in the intervention group. CONCLUSION: Endometrial injury improves the outcome of the subsequent IVF treatment cycle. Large and robust randomized trials comparing endometrial injury with no intervention before IVF treatment are needed to further guide clinical practice.
P-577 Wednesday, October 19, 2011 ENDOMETRIAL INJURY VIA SALINE-INFUSION SONOHYSTEROGRAM (SIS) PERFORMED WITHIN ONE MONTH OF CYCLE START DOES NOT IMPROVE LIVE BIRTH RATE. M. C. Peavey, A. A. Shah, D. J. Raburn, D. K. Walmer, S. D. Copland, T. M. Price. Duke Fertility Center, Duke University Medical Center, Durham, NC. OBJECTIVE: Approximately two-thirds of implantation failures following in vitro fertilization (IVF) are due to inadequate uterine receptivity.
S277