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(weighted mean difference-WMD). The StatsDirect® statistical software (Cheshire, UK) was used for data analysis. RESULTS: Five trials fulfilled the inclusion criteria (Levi-Setti et al 2005, Griesinger et al 2005, Sauer et al 2004, Acevedo et al 2004, CedrinDurnerin et al 2004). In 3 trials, the multiple low-dose (0.25mg) antagonist regimen was applied. The others 2 trials, the single dose (3mg) antagonist regimen were applied. All trials compared ovarian stimulation with r-FSH alone (control group) versus ovarian stimulation with r-FSH ⫹ r-LH (study group). In 4 trials r-LH was beginning at the same day of GnRH antagonist and in one trial at the beginning of the ovarian stimulation. When the meta-analysis was carried out we observed advantages for the LH supplementation protocol with respect to a higher serum estradiol levels on the day of HCG administration (p⬍0.0001; WMD: 514, 95% CI: 368, 660) and higher number of mature oocytes (p⫽0.0098; WMD:0.88, 95% CI: 0.21, 1.54). However, these differences were not observed in days of stimulation (p⫽0.65; WMD:0.07 95% CI: -0.24, 0.37), total dose of r-FSH administered (p:0.87; WMD:8.51, 95% CI: -98.2, 115.2), number of oocyte retrieval (p:0.34; WMD:0.41, 95% CI: -0.44, 1.3), the CPR per oocyte retrieval (p:0.69; OR 0.89, 95% CI: 0.57, 1.39), the implantation rate (p:0.96; OR:0.99 95% CI: 0.66, 1.48) and miscarriage rate (p:0.82; OR 1.06, 95% CI: 0.29, 3.8). CONCLUSION: In the IVF/ICSI cycles the use GnRH antagonist protocol with r-LH supplementation to r-FSH induces to higher serum level of estradiol in the day of HCG and gives higher number of MII oocytes. However, cycles with or without r-LH supplementation spent similar time for ovarian stimulation and similar amount of r-FSH, give similar total number of oocytes retrieved and achieve similar pregnancy, implantation and miscarriage rates Supported by: None

CONCLUSION: Rising total dosages of exGn administered in COH cycles did not compromize embryo quality or pregnancy outcomes (Table 1). Furthermore, with appropriate age correction (Table 2), increasing dosages of exGn/oocyte retrieved were not consistently associated with compromized pregnancy outcome. Our analysis indicates that any association between exGn dosages and pregnancy outcomes would be primarilly mediated by age-induced ovarian insensitivity to exGn, with no direct impact of exGn on pregnancy outcome. Supported by: None

P-756 P-757 THE IMPACT OF DOSAGES OF EXOGENOUS GONADOTROPINS (EXGN) ON OUTCOMES OF CYCLES OF CONTROLLED OVARIAN HYPERSTIMULATION (COH). B. A. Stone, J. M. Vargyas, G. E. Ringler, C. M. March, R. P. Marrs. California Fertility Partners, Los Angeles, CA. OBJECTIVE: To establish whether claimed compromizing effects of exGn on the uterine environment and on pregnancy outcomes are related solely to the total dosages of exGn, or are related to an underlying ovarian insensitivity to exGn which necessitated higher dosages. DESIGN: Retrospective analysis of properties of COH cycles, embryo quality and pregnancy outcomes. MATERIALS AND METHODS: Data were analyzed from 1302 consecutive GnRHa down-regulation/ COH cycles in women ⱕ40 years of age which resulted in embryo transfer (ET). Cycles were grouped by total exGn dosages and by exGn dosages/oocyte. Outcomes were compared by Chi2; differences in properties of the COH and of the oocyte/embryo parameters were analyzed by ANOVA (3x3 factorial, partitioned as in table). RESULTS: In Table 1, pregnancy rates in the same row, or in the same column, followed by the same letter differ significantly. Within columns, pregnancy rates fell with rising exGn dosages/recovered oocyte, coincident with increasing patient age. Within rows, neither pregnancy rates nor patient ages differed with changing total dosages of exGn/cycle. Average numbers of oocytes recovered increased in proportion to rising total exGn dosages, while rates of E2 rise did not vary.Within columns, daily E2 rises decreased as the amps/oocyte increased (from 55 to 44%/day), verifying rising ovarian insensitivity to exGn. Fertilization rates did not differ between cells. Average numbers of blastomeres in all, and in transferred, embryos did not differ within rows, but decreased (from 7.4 to 6.2; P⬍0.0001) as the amps/oocyte increased. Similarly, average embryo grades were constant within rows, but decreased (P⬍0.0001) as amps/oocyte increased. Average numbers of embryos transferred did not differ between cells. With respect to the close association between amps exGn/oocyte and patient age, cycles were further subdivided by age (Table 2). Within age categories, there were no consistent correlations between exGn dosages/oocyte and pregnancy outcome.

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Abstracts

HUMAN CUMULUS CELLS GENE EXPRESSION PROFILE OF MODIFIED NATURAL CYCLE COMPARED TO MILD STIMULATED ANTAGONIST PROTOCOL IN YOUNG POOR RESPONDER PATIENTS. S. Gasca, V. Loup, L. Reyftman, F. Pellestor, J. De Vos, S. Hamamah. CHU-Montpellier, Service de Biologie de la Reproduction B, Montpellier F-34295, France; CHU Montpellier, Institut de Recherche en Biothe´rapie, Hoˆpital Saint-Eloi, Montpellier F-34295, France. OBJECTIVE: There is no standard protocol for poor responder patients referred for in vitro fertilization program. In this case, the spontaneous cycle has the advantage not to interfere with natural ovarian recruitment and selection, and therefore yielding better quality oocytes. Cumulus cells offer the possibility to identify markers that are altered in poor responder patients. The aim of this study is to determine human cumulus gene expression profile in two randomized groups: modified natural cycle (MNC) and mild stimulated cycle (MSC) groups. DESIGN: Extraction of RNA from cumulus cells collected from patients following an ART program and displaying a poor response to ovarian stimulation. Gene expression and statistical analyses using human cDNA microarray chips technology. MATERIALS AND METHODS: The patients were randomized in two groups: MNC (recFSH 150 IU and GnRH antagonist 0.5 mg/day were started concomitantly when a follicle with a diameter of 14 mm was present at ultrasound) and MSC (recFSH 150 IU was started upon day 5 and GnRH antagonist 0.25 mg/day was started when follicles with a mean diameter of 14 mm were present). hCG 10 000 IU was administrated as soon as the mean follicular diameter was ⱖ 16 mm in both groups. Egg collection was made 36 hours post hCG. The cumulus cells were mechanically removed on day 0 and frozen at -80°C in RLT buffer from the RNeasy kit (Qiagen) before RNA extraction. Pools of cumulus cells from a single patient were analyzed on Affymetrix™ HG-U133 plus 2.0 GeneChip oligonucleotide array chips made of 54675 probesets and representing roughly 35000 unique human known or predicted genes. The Affymetrix™ GeneChip Operating Software 1.2 (GCOS) was used to evaluate the signal intensity for each probeset (detection call“present” or “absent”) and also to perform pair wise comparison between single gene expression raw values. Differential expression was determined by selecting the probesets with the following constraints: ratios ⱖ

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3 with a significant change p-value (P ⱕ 0.01), “overexpressed” probeset “present” with a signal value ⱖ 20. RESULTS: Roughly most of the genes detected are present in both groups (n⫽ 11750). Interestingly, genes (GREM1, HAS2 and PTGS2) that have previously been identified has markers concomitant with a normal embryo development, are expressed at higher levels in MSC than in MNC. In addition, MSC cumulus cells upregulated a number of genes: PRB-1 & -4, NTS, PCD6, DKK1 (a negative regulator of the Wnt pathway), HSD17B1 (estrogen regulation), PTGS-1 & -2 , CD151, CD44, D200, PTGER2 (generally upregulated in human cumulus cells, as reported by Assou et al. 2006). In MNC cumulus cells, the strongest upregulation was observed for the interleukin receptor ILR1 and for IL8, CFH & CFHL1 (complement factor), EGR4, CTGF, CXCL2, RORB, ADLICAN, ITM2A and NRXN3. CONCLUSION: When comparing poor responder patients with normal responders, the expression profile of cumulus cells from the MNC group is slightly altered. On the other hand, expression of cumulus expansion and maturation genes such as HAS2 and PTGS is normal in MSC cumulus cells and recurrently higher than the one found in the MNC group. Thus evaluating the relationships between ovarian stimulation and cumulus cell gene expression profile in poor responders will permit to develop individually tailored stimulation protocols greatly improving the success of in vitro fertilization. Supported by: Ferring Pharmaceuticals

P-758 A COMPARISON OF PREGNANCY RATES FOLLOWING FRESH AND FROZEN EMBRYO TRANSFER ACCORDING TO THE USE OF LEUPROLIDE ACETATE VS. GANIRELIX VS. CETRORELIX. B. Katsoff, J. H. Check, C. Wilson, J. K. Choe, J. Amui. UMDNJ, Robert Wood Johnson Med. School at Camden, Marlton, NJ. OBJECTIVE: Debate still exists as to whether gonadotropin releasing hormone (GnRH) antagonists somewhat impair pregnancy rates compared GnRH agonists. The present study retrospectively compared pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) in cycles using GnRH agonists for controlled ovarian hyperstimulation (COH) vs. agonists. Furthermore the study would determine if any differences exist between the two antagonists (ganirelix vs. cetrorelix) on pregnancy rates. Finally by evaluating fresh and frozen ET pregnancy rates with the two antagonists and the one agonist (leuprolide acetate) if an adverse effect was found, these comparisons would help to determine if the adverse effect is on the uterine environment or the embryo itself. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: First IVF cycles in our IVF center from 1/02 to 11/05 were the source of the study population. Age requirements of the female partner was ⱕ39.9 and only IVF cycles with ⱖ5 eggs retrieved were included. The cycles were stratified as to whether the COH protocol used an antagonist vs. agonist. The antagonist group was further stratified as to the use of ganirelix vs. cetrorelix. The leuprolide acetate was started mid-luteal phase 10 IU for 10 days then 5 IU through the follicular phase. The antagonists were started with a 14mm follicle 250mcg per day. Various brands of gonadotropins were used. RESULTS: The pregnancy outcome of both first fresh and frozen ET is seen in the table below. There was a significantly lower clinical pregnancy rate per transfer with ganirelix vs. either cetrorelix or leuprolide acetate following fresh or frozen ET. However because of lower miscarriages there was only a non-significant trend for lower ongoing delivered pregnancy rates. The implantation rates were also significantly lower for ganirelix following fresh transfer (21.7%) compared to cetrorelix (26.8%) and leuprolide acetate (28.4%). Similarly the implantation rates were significantly lower with ganirelix (14.1%) vs. cetrorelix (24.7%) and leuprolide acetate (20.2%) (p⬍.01, p⬍.01)

CONCLUSION: For unexplained reasons COH protocols using the antagonist ganirelix yield lower pregnancy and implantation rates than using the antagonist cetrorelix or the agonist leuprolide acetate. The fact that the frozen ET pregnancy and implantation rates were also lower suggest that the adverse effect may be on the embryo rather than the endometrium. Supported by: None

P-759 LOW DOSE GNRH-A PROTOCOL VERSUS GNRH ANTAGONIST PROTOCOL IN THE MANAGEMENT OF POOR RESPONDERS UNDERGOING IVF. M. A. Melo Sr., C. E. Busso Sr., J. Domingo Sr., S. R. Soares Sr., J. Remohı´ Sr., A. Pellicer Sr. Instituto Valenciano de Infertilidad, Valencia, Spain. OBJECTIVE: The aim of this study was to compare a low dose GnRH-a protocol with a GnRH antagonist protocol in poor responders undergoing IVF treatment. DESIGN: Retrospective study. MATERIALS AND METHODS: We have studied 467 second ovarian stimulation cycles in women who had had their first cycles cancelled due to a poor response (less than 4 oocytes retrieved) using a standard GnRH-a long protocol. This protocol consisted of leuprolide acetate given from the mid-luteal phase at 1.0 mg sc daily until menses, and then 0.5 mg daily until the morning of hCG administration. Second cycles were carried out between January 2000 and September 2005. A total of 92 patients were stimulated using a GnRHa low dose protocol (Group I), that consisted of 0.5 mg leuprolide acetate daily started in the mid-luteal phase. When ovarian quiescence was confirmed by vaginal ultrasound, dose was reduced to 0.25 mg. GnRH antagonist protocol was performed in the remaining 375 patients (Group II). rFSH 375 IU daily, in both groups, was started on the 3rd day of the menstrual cycle. Gonadotrophin dose was adjusted according to E2 levels and follicle development. Cetrorelix (0.25 mg, sc, daily) was started on day 6 of the stimulation until the day of hCG administration. Ovulation was triggered with 6500 IU of hCG sc when the leading follicles reached 18mm. Oocyte retrieval was scheduled 36 hours later. Groups were compared regarding COH parameters and IVF outcome. RESULTS: No significant difference was observed between groups regarding patient’s age (35.8 vs. 36.1 years), duration of stimulation (10.4 vs. 9.7 days), and total gonadotrophin dose (3919 IU vs. 3555 IU). The number of oocytes retrieved was significantly higher in Group I (9.1 vs. 6.0, p⫽ 0.001) and cancellation rate was significantly lower (14.1% vs. 23.8%, p⫽0.04). No significant difference was observed in fertilization rate (81% vs. 79.3%) and number of replaced embryos (1.9 vs. 2.1). Implantation rate was higher in Group II (34.3% vs. 24%) and this difference was close to significance (p⫽0.05). Pregnancy rate per cycle initiated was not different between groups (31.5% vs. 31.2%). Pregnancy rate per transfer and miscarriage rate were higher in Group II, but these differences did not reach statistical significance (50.9% vs. 41.7% and 21.3% vs. 13.3%, respectively). CONCLUSION: In patients with a first IVF cycle cancelled due to low response using long GnRH-a protocol, pregnancy probability in a second cycle is the same either using a low dose GnRH-a protocol or a GnRH antagonist protocol. Supported by: None.

P-760 EVIDENCE THAT HIGH SERUM PROGESTERONE (P) LEVELS ON DAY OF HUMAN CHORIONIC GONADOTROPIN (HCG) INJECTION HAVE NO ADVERSE EFFECT ON THE EMBRYO ITSELF AS DETERMINED BY PREGNANCY OUTCOME FOLLOWING DONOR EMBRYO TRANSFER. J. H. Check, C. Wilson, J. K. Choe, J. Amui, D. Brasile. UMDNJ, Robert Wood Johnson Med. School at Camden, Marlton, NJ. OBJECTIVE: There is evidence that a premature rise in P on the day of hCG injection has an adverse effect on pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET). The objective of the present study was to determine pregnancy outcome in recipients according to the P level of the donor at the time of hCG injection. Lower pregnancy rates with advancing P levels would suggest that the adverse effect of P is on the

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