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The role of endometrial function test (EFT®) in recurrent implantation failure (RIF) in IVF
to the cell culture for 48 hours and conditioned media were collected. The concentration of IL-1a, IL-1b, IL-1ra, IL-6, TGF-b, FGF, IFN-g, IL-17, VEGF, EGF, Leptin were detected simultaneously by Luminex bead analysis and their levels before and after mifepristone treatment were compared. RESULTS: The level of IL-1ra, IL-6, FGF, VEGF was increased significantly (P<0.01) while the level of IL-1b, EGF, Leptin, TGF-b were decreased significantly (P<0.05) after treatment of mifepristone. Mifepristone had no effect on the expression level of IL-1a, IFN-g, IL-17 in the decidual stromal cells.
GnRH-agonist and antagonist cycles show no differences in IRs among E2 subgroups. CONCLUSIONS: Our study suggest that higher E2 level during COH with GnRH-agonist and antagonist cycle does not affect implantation potential. Lower PR in antagonist than in agonist cycles may not be due to significantly lower E2 level on hCG administration. Supported by: None.
P-163 TABLE
Cytokines and growth factors IL-1a IL-1b IL-1ga IL-6 IL-17 IFN-g VEGF EGF FGF Leptin TGF-b
DSC
DSC þ RU486
P value
0.4529 0.04 1.97 0.13 31.64 1.59 82.63 6.40 0.46 0.03 0.30 0.02 1.41 0.08 1.56 0.12 2.54 0.21 430.11 17.02 362.86 46.45
0.51 0.05 1.42 0.16 141.52 5.92 388.98 20.76 0.49 0.03 0.32 0.04 153.95 8.53 1.43 0.05 9.44 0.38 84.58 2.53 144.29 15.12
0.092 0.000 0.000 0.000 0.191 0.140 0.000 0.011 0.000 0.000 0.000
CONCLUSIONS: The antigestational effect of mifepristone might act through down- regulating the expression of IL-1b,, EGF, Leptin, TGFb and up-regulating expression of IL-1ra, IL-6, FGF, VEGF, which interfered with the decidualization process. Mifepristone may enhance immune rejection to fetus and promote apoptosis of decidua that induce the termination of early pregnancy. Supported by: National Natural Science Foundation of China (30470657) and Natural Science Foundation of Gunangdong (04020416).
P-162 COMPARISON OF IMPLANTATION RATE BETWEEN GNRH AGONIST AND ANTAGONIST CYCLES ACCORDING TO E2 LEVEL. C. W. Park, K. M. Yang, J. Y. Kim, M. K. Koong, I. S. Kang, I. O. Song. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong Univ. College of Medicine, Seoul, Korea. OBJECTIVE: High E2 level during COH in both GnRH-agonist and antagonist cycles may affect embryo implantation, while E2 level on hCG is higher in GnRH agonist than in antagonist cycles. GnRH antagonist cycles have been reported a lower pregnancy (PR) and implantation rate (IR) than agonist cycles. To evaluate whether lower E2 level on hCG in GnRH-antagonist cause lower implantation potential than GnRH-agonist cycles, we compare IR between two groups according to E2 level on hCG administration. DESIGN: Retrospective controlled study. MATERIALS AND METHODS: From July 2003 to Feburary 2007 IVFET cycles with GnRH-agonist (n ¼ 806) and with antagonist (n ¼ 312) were retrospectively analysed. IVF-ET cycles which indication have been reported lower implantation potential : PCOS, endometriosis III, IV, non-obstructive azoospermia and advanced age (R38 years) were excluded in this study. E2 level on hCG administration was subgrouped per 500pg/ml ranging from 1250 to 3750 pg/ml and IR was compared between two groups according to E2 subgroups. Statistical analysis was performed using Student t-test and Chi-square, P<0.05 was considered as statistically significant. RESULTS: There was significant difference in E2 level on hCG administration between GnRH-agonist and antagonist cycles (2216.5 1193.52pg/ ml vs. 1497.4 948.17pg/ml, P<0.001). There were no significant differences in mean age of patents (32.0 vs. 32.6), No. of transferred embryo (3.3 vs. 3.1) and endometrial thickness on hCG (11.0 vs. 10.5mm) between two group. The PR was 43.7% vs. 41.7% without significant difference. IR shows no significant difference between two groups in each E2 subgroup : 19.8% vs. 19.1% (1250%E2<1750 pg/ml); 22.4% vs. 24.4% (1750%E2< 2250 pg/ml); 18.7% vs. 17.3% (2250%E2<2750 pg/ml); 18.7% vs. 16.7% (2750%E2<3250 pg/ml); 23.7% vs. 28.8% (3250%E2<3750 pg/ml). The
S162
Abstracts
THE ROLE OF ENDOMETRIAL FUNCTION TEST (EFTÒ) IN RECURRENT IMPLANTATION FAILURE (RIF) IN IVF. E. B. JohnstonMacAnanny, H. J. Kliman, D. B. Maier, J. C. Nulsen, C. A. Benadiva. The Center for Advanced Reproductive Services, University of Connecticut Health Center, Farmington, CT; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT. OBJECTIVE: Patients with RIF merit endometrial investigation. The EFTÒ evaluates cyclin E and p27, endometrial proteins which may be involved with implantation. The aim of this study was to determine the predictive value of EFTÒ in IVF patients with RIF for future pregnancy. DESIGN: A retrospective chart review of endometrial function tests performed for RIF (>or equal to 2 IVF cycles with no conception with good quality embryos) in the IVF setting was performed at an academic medical center. MATERIALS AND METHODS: All patients undergoing EFTÒ for RIF were identified. EFTÒ involves immunohistochemical staining of the endometrium with markers for mitotic regulators cyclin E and p27 (an inhibitor of cyclin E.) Typically, cyclin E is only found in the proliferative and the early secretory phases and P27 is found only in the secretory phase. Both mock and natural EFTÒ cycles were evaluated. In mock cycles patients underwent GnRH down regulation and received supplemental transdermal estrogen and vaginal progesterone prior to the biopsy with a standardized protocol. Natural cycles were cycles devoid of supplementation. Abnormal biopsies were defined as inappropriately elevated cyclin E expression in the luteal phase. Subsequent pregnancies in cycles following the EFTÒ were recorded. Chi square analysis was performed. RESULTS: Patients had 36 biopsies (Table 1, 2). For patients with natural cycle biopsies, subsequent pregnancy rates were high and not affected by biopsy result. For patients with mock cycle biopsies, subsequent pregnancy rates were similiarly high in patients with normal biopsies. No subsequent pregnancies were seen in the patients with abnormal mock cycle biopsies, however the numbers were too small to meet statistical significance.
TABLE 1. Natural cycle biopsies
Biopsy result Normal Abnormal
# Biopsies
Clinical pregnancy rate (%)
12 12
70.0 (7/10) 72.7 (8/11)
P¼0.89, 3 patients did not pursue further treatment. TABLE 2. Mock cycle biopsies
Biopsy result Normal Abnormal
# Biopsies
Clinical pregnancy rate (%)
9 3
62.5 (5/8) 0 (0/2)
P¼0.11, 2 patients did not pursue further treatment. CONCLUSIONS: EFTÒ in the natural cycle does not predict subsequent pregnancy in our subjects. Our data suggest a trend to support the predictive value of a mock cycle abnormal EFTÒ in future pregnancy, however this was not statistically significant given the small number of subjects. Further work is needed to clarify the role of endometrial abnormalities in RIF. Supported by: None.
Vol. 88, Suppl 1, September 2007
GnRH-agonist and antagonist cycles show no differences in IRs among E2 subgroups. CONCLUSIONS: Our study suggest that higher E2 level during COH with GnRH-agonist and antagonist cycle does not affect implantation potential. Lower PR in antagonist than in agonist cycles may not be due to significantly lower E2 level on hCG administration. Supported by: None.
P-163 TABLE
Cytokines and growth factors IL-1a IL-1b IL-1ga IL-6 IL-17 IFN-g VEGF EGF FGF Leptin TGF-b
DSC
DSC þ RU486
P value
0.4529 0.04 1.97 0.13 31.64 1.59 82.63 6.40 0.46 0.03 0.30 0.02 1.41 0.08 1.56 0.12 2.54 0.21 430.11 17.02 362.86 46.45
0.51 0.05 1.42 0.16 141.52 5.92 388.98 20.76 0.49 0.03 0.32 0.04 153.95 8.53 1.43 0.05 9.44 0.38 84.58 2.53 144.29 15.12
0.092 0.000 0.000 0.000 0.191 0.140 0.000 0.011 0.000 0.000 0.000
CONCLUSIONS: The antigestational effect of mifepristone might act through down- regulating the expression of IL-1b,, EGF, Leptin, TGFb and up-regulating expression of IL-1ra, IL-6, FGF, VEGF, which interfered with the decidualization process. Mifepristone may enhance immune rejection to fetus and promote apoptosis of decidua that induce the termination of early pregnancy. Supported by: National Natural Science Foundation of China (30470657) and Natural Science Foundation of Gunangdong (04020416).
P-162 COMPARISON OF IMPLANTATION RATE BETWEEN GNRH AGONIST AND ANTAGONIST CYCLES ACCORDING TO E2 LEVEL. C. W. Park, K. M. Yang, J. Y. Kim, M. K. Koong, I. S. Kang, I. O. Song. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong Univ. College of Medicine, Seoul, Korea. OBJECTIVE: High E2 level during COH in both GnRH-agonist and antagonist cycles may affect embryo implantation, while E2 level on hCG is higher in GnRH agonist than in antagonist cycles. GnRH antagonist cycles have been reported a lower pregnancy (PR) and implantation rate (IR) than agonist cycles. To evaluate whether lower E2 level on hCG in GnRH-antagonist cause lower implantation potential than GnRH-agonist cycles, we compare IR between two groups according to E2 level on hCG administration. DESIGN: Retrospective controlled study. MATERIALS AND METHODS: From July 2003 to Feburary 2007 IVFET cycles with GnRH-agonist (n ¼ 806) and with antagonist (n ¼ 312) were retrospectively analysed. IVF-ET cycles which indication have been reported lower implantation potential : PCOS, endometriosis III, IV, non-obstructive azoospermia and advanced age (R38 years) were excluded in this study. E2 level on hCG administration was subgrouped per 500pg/ml ranging from 1250 to 3750 pg/ml and IR was compared between two groups according to E2 subgroups. Statistical analysis was performed using Student t-test and Chi-square, P<0.05 was considered as statistically significant. RESULTS: There was significant difference in E2 level on hCG administration between GnRH-agonist and antagonist cycles (2216.5 1193.52pg/ ml vs. 1497.4 948.17pg/ml, P<0.001). There were no significant differences in mean age of patents (32.0 vs. 32.6), No. of transferred embryo (3.3 vs. 3.1) and endometrial thickness on hCG (11.0 vs. 10.5mm) between two group. The PR was 43.7% vs. 41.7% without significant difference. IR shows no significant difference between two groups in each E2 subgroup : 19.8% vs. 19.1% (1250%E2<1750 pg/ml); 22.4% vs. 24.4% (1750%E2< 2250 pg/ml); 18.7% vs. 17.3% (2250%E2<2750 pg/ml); 18.7% vs. 16.7% (2750%E2<3250 pg/ml); 23.7% vs. 28.8% (3250%E2<3750 pg/ml). The
S162
Abstracts
THE ROLE OF ENDOMETRIAL FUNCTION TEST (EFTÒ) IN RECURRENT IMPLANTATION FAILURE (RIF) IN IVF. E. B. JohnstonMacAnanny, H. J. Kliman, D. B. Maier, J. C. Nulsen, C. A. Benadiva. The Center for Advanced Reproductive Services, University of Connecticut Health Center, Farmington, CT; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT. OBJECTIVE: Patients with RIF merit endometrial investigation. The EFTÒ evaluates cyclin E and p27, endometrial proteins which may be involved with implantation. The aim of this study was to determine the predictive value of EFTÒ in IVF patients with RIF for future pregnancy. DESIGN: A retrospective chart review of endometrial function tests performed for RIF (>or equal to 2 IVF cycles with no conception with good quality embryos) in the IVF setting was performed at an academic medical center. MATERIALS AND METHODS: All patients undergoing EFTÒ for RIF were identified. EFTÒ involves immunohistochemical staining of the endometrium with markers for mitotic regulators cyclin E and p27 (an inhibitor of cyclin E.) Typically, cyclin E is only found in the proliferative and the early secretory phases and P27 is found only in the secretory phase. Both mock and natural EFTÒ cycles were evaluated. In mock cycles patients underwent GnRH down regulation and received supplemental transdermal estrogen and vaginal progesterone prior to the biopsy with a standardized protocol. Natural cycles were cycles devoid of supplementation. Abnormal biopsies were defined as inappropriately elevated cyclin E expression in the luteal phase. Subsequent pregnancies in cycles following the EFTÒ were recorded. Chi square analysis was performed. RESULTS: Patients had 36 biopsies (Table 1, 2). For patients with natural cycle biopsies, subsequent pregnancy rates were high and not affected by biopsy result. For patients with mock cycle biopsies, subsequent pregnancy rates were similiarly high in patients with normal biopsies. No subsequent pregnancies were seen in the patients with abnormal mock cycle biopsies, however the numbers were too small to meet statistical significance.
TABLE 1. Natural cycle biopsies
Biopsy result Normal Abnormal
# Biopsies
Clinical pregnancy rate (%)
12 12
70.0 (7/10) 72.7 (8/11)
P¼0.89, 3 patients did not pursue further treatment. TABLE 2. Mock cycle biopsies
Biopsy result Normal Abnormal
# Biopsies
Clinical pregnancy rate (%)
9 3
62.5 (5/8) 0 (0/2)
P¼0.11, 2 patients did not pursue further treatment. CONCLUSIONS: EFTÒ in the natural cycle does not predict subsequent pregnancy in our subjects. Our data suggest a trend to support the predictive value of a mock cycle abnormal EFTÒ in future pregnancy, however this was not statistically significant given the small number of subjects. Further work is needed to clarify the role of endometrial abnormalities in RIF. Supported by: None.
Vol. 88, Suppl 1, September 2007