reduction of 18% for FAQ was suggested by the manufacturer (2). Since a prospective comparison is not possible due to the discontinuation of FP, we compared retrospectively the outcome of IVF/ICSI cycles treated with both formulations in our center. Our objectives were (1) to compare treatment outcomes for patients treated with either formulation and (2) to determine if a lower starting dose translated into a lower overall treatment dose without affecting outcome. DESIGN: Retrospective analysis of 468 IVF/ICSI cycles MATERIALS AND METHODS: Four hundred sixty-eight patients enrolled in our ART program between January 1st, 2004 and January 31st, 2005, were included in the study. Patients were down-regulated with the standard mid-luteal leuprolide protocol. Controlled ovarian hyperstimulation (COH) started with 225-300 IU of reconstituted FP using a traditional syringe (Group1) or 200-275 IU FAQ using a pen device (Group 2). After five days of treatment follicular response was evaluated and dose adjusted accordingly. When the leading follicle achieved ⬎18mm and at least two others 16mm with appropriate E2 (100-200 pg/follicle ⬎14mm), final follicle maturation was triggered with 250 mcg of r-hCG. Oocyte retrieval was scheduled for 34-36 hours later. Luteal phase support was provided for all patients. Statistical analysis was done using Student’s T test, Chi-square or Fisher’s exact test as required. Statistical significance was set at a p-value ⬍0.05. RESULTS: There were no significant differences for age, BMI, total dose of r-hFSH utilized, peak E2, number of follicles ⬎12mm, total and mature oocytes retrieved and the number fertilized normally. Patients treated with an initial reduced starting dose of FAQ required on average 0.7 more days of treatment. The number of embryos transferred, implantation and pregnancy rates were statistically higher in favor of FP, Group 1.
MATERIALS AND METHODS: A subgroup of PCOS women aged 20-29 yrs(n: 28) whose at least 2 consecutive OI/IUI cycles were cancelled due to premature LH surge were included in the study. All received recombinant FSH and GnRH antagonist (Ganirelix ) at a dose of 0.25 mg per day starting on the day in which a leading follicle ⱖ13 mm in mean diameter was visualized, until hCG administration. All of the couples had infertility work up, including spermiogram and hysterosalpingography. PCOS patients were diagnosed according to the revised diagnostic criteria for PCOS in 2003. Four patients with body mass indexes(BMI) ⬎30kg/m2 were excluded from the study group. Insemination was performed 34 h after hCG injection. RESULTS: No premature LH surge was observed in GnRH antagonist administered cycles. The regimen with GnRH antagonist administration was associated with increased rate of monoovulation and higher clinical pregnancy rate per initiated cycle ( 65% and 32% , respectively). One multiple pregnancy and no OHSS was observed CONCLUSION: Endocrinological alterations observed in PCOS remains a major problem both in obtaining optimal ovulation induction and implantation. Despite the protocols used premature LH surge /cancelled cyles and hyperstimulation is frequently observed. Thus increasing the cost and stress of the treated couples suitable for OI/IUI. Adding GnRH antagonis to OI/IUI cycles IN PCOS patients with previous cancelled cycles with premature LH surge, is found to be costeffective in both optimizing the OI cycle and improving the pregnancy rates. Supported by: None
P-425 Don’t Push Too Hard! High Intensity Controlled Ovarian Hyperstimulation Does not Greatly Improve Blastulation Rates or Blastocyst Pregnancy Rates. T. Mukherjee, A. Copperman, B. Sandler, L. Grunfeld, J. Barritt, M. Duke. Reproductive Medicine Associates of NY, Mt Sinai Hospital, New York, NY.
CONCLUSION: The results of this study showed that the total amount of drug utilized was not significantly different between the groups. This indicated that lowering the starting dose of FAQ as recommended by the manufacturer did not impact the total amount of r-hFSH/cycle. Total days on FSH treatment, pregnancy and implantation rates were significantly higher for FP versus FAQ. In conclusion lowering the initial dose of Follistim® AQ did not translate into lower overall treatment dose, less treatment days or better cycle outcome compared to FP. We are currently assessing the use of a higher initial dose of FAQ in our center. Supported by: None References: 1. Voortman G, 1999, Hum Reprod. Jul;14(7): 1698-702 2. Follistim AQ Package insert P-424 Effectiveness of GnRH Antagonist Use in PCOS Patients With Repeated Premature LH Surge in Patients Undergoing IUI Cycles. O. Taskin, M. Erman Akar, S. Kursun, Z. Salar, T. Gunduz, M. Uner. Akdeniz University School of Medicine, Antalya, Turkey. OBJECTIVE: The cost-effectiveness of GnRH antagonists in patients undergoing stimulation (OI) for intrauterine insemination needs to be determined. We aimed to outline the effectiveness of GnRH antagonist use in PCOS patients with repetaed premature LH surge in previous IUI cycles. DESIGN: Prospective clinical trial
FERTILITY & STERILITY威
OBJECTIVE: Appropriate controlled ovarian hyperstimulation is essential for optimal outcome in assisted reproduction. With the advent of improved in vitro culture systems, a greater emphasis is being placed on blastocyst transfer with its reduced multiple pregnancy rate and utility in cycles requiring preimplantation genetic diagnosis. Clinically, it is tempting to increase the intensity of stimulation in an attempt to increase oocyte number, and maximize the likelihood of blastocyst transfer .. Of course, this in turn increases the risk of ovarian hyperstimulation and the costs and morbidity associated with OHSS. We undertook this study in effort to correlate blastulation rates and pregnancy rates with intensity of stimulation. DESIGN: Retrospective analysis of assisted reproduction outcomes in a large academic center MATERIALS AND METHODS: A retrospective analysis of 1143 consecutive women undergoing assisted reproduction using the down regulation protocol between August 2002 and December 2004 was undertaken. Variables analyzed included peak estradiol, oocytes retrieved, 2PN embryos, blastulation rate, and blastocyst pregnancy rate. Continuous variables were assessed by Student’s t-test or Wilcoxon rank sum test if data did not appear normally distributed. Categorical variables were assessed by Chisquare test or two tailed- Fisher’s exact test in the case of small cell frequencies. A P-value of 0.05 was considered statistically significant. RESULTS: The indications for IVF were tubal (n⫽397), male (n⫽268), anovulation (n⫽102), endometriosis (n⫽86), ovarian dysfunction (84), and mixed (n⫽206). ICSI (n⫽205) was performed for couples with severe semen abnormalities (less than 106 motile spermatozoa were recovered after sperm preparation. ICSI was also performed in cases of testicular sperm extraction from the epididymis or testes. Blastulation rates were lower in patients with a peak estradiol under 2000 pg/mL (table). Mean oocyte number and count of 2PN embryos were also lower in patients with peak estradiol under 2000 pg/mL(table). However pregnancy rates were similar in all groups. Table Comparison of blastulation rate, blast pregnancy rate, oocytes retrieved, and 2PN embryos by peak estradiol value P⬍0.05 CONCLUSION: Blastocyst transfer is effective in maximizing pregnancy rates and minimizing the chance of higher order multiple gestations. Patients with peak estradiol values above 2000 pg/mL had comparable rates of blastulation, and no significant increase in blastulation rate, number of oocytes or 2PN embryos when compared to patients with peak estradiol of 2500 or greater. Pregnancy rates were similar in all groups. High intensity controlled ovarian hyperstimulation is not necessary to achieve excellent
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P-427 Effectiveness of Using GnRH Antagonist Protocol With Unsuccessful Long Protocol GnRH Agonist Cases (Full Term Pregnancies Had Not Resulted) in In-Vitro Fertilization (IVF) Cycles. A. Yoshida, M. Kakinuma, T. Matsuba, H. Suzuki, A. Takahashi, M. Tanaka. Kiba Park Clinic, Tokyo, Japan.
pregnancy rates. By avoiding peak estradiol values over 3000 pg/mL the risk of severe ovarian hyperstimulation can be reduced, and the benefits of blastocyst culture and transfer safely realized. Supported by: None P-426 A Comparison Between the New Follitropin Alfa Filled by Mass and the Follitropin Alfa Filled by Bioassay in the Same Egg Donors. G. Martinez, J. Sepulveda, A. Arici, J. Dorey, P. Patrizio. Yale University, New Haven, CT. OBJECTIVE: To compare the ovarian stimulation characteristics of the new follitropin alfa filled by mass (r-hFSH-fbm) vs. the conventional follitropin alfa filled by bioassay (r-hFSH-bio) in the same egg donor patients. DESIGN: Retrospective observational MATERIALS AND METHODS: From our egg donor program we identified 9 donors who had two egg retrieval cycles, one with r-hFSH-bio (Gonal-f Multidose ®) and other one with r-hFSH-fbm (Gonal-f RFF ®), acting as their own control, for a total of 18 cycles. The protocol of ovarian stimulation was exactly the same in both cycles consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with r-hFSH alfa. Data collected comprised of age, BMI, total days and total amount of r-hFSH, E2 levels at hCG, follicular numbers and diameters, number of oocytes retrieved, fertilized, cleavage and embryo quality. Data was analyzed by JMP 5.0 software with paired T-test for continuous variables and Chi-square test for categorical data as appropriate; significance was set up at p ⬍0.05. RESULTS: The results summarized in the table are expressed as mean ⫾ standard deviation. The Estradiol peak was statistically higher with the r-hFSH-fbm than with r-hFSH-bio (2,887 vs 2361 pg/ml) (p ⬍ 0.05). The total amount of FSH utilized, the number of follicles ⬎14 mm, oocytes retrieved, eggs fertilized, cleavage embryos and the total number of embryos at day 3 or 5, showed a positive trend in favor of r-hFSH-fbm , although the differences did not reach statistical significance.
OBJECTIVE: Since GnRH antagonist became available it has been possible to select between two methods: GnRH agonist protocol and GnRH antagonist protocol. At our clinic the long protocol, using GnRH agonist, has been the first choice for good responders, and the GnRH antagonist protocol has been the first choice for poor responders. The aim of this study was to consider the effectiveness of using antagonist protocol with unsuccessful cases (full term pregnancies had not resulted) even though the long protocol had been carried out with good responders. DESIGN: Retrospective. MATERIALS AND METHODS: The subjects were 66 cases on whom IVF was carried out (148 cycles: 72 cycles with long protocol and 76 cycles with antagonist protocol). All the cases had been unsuccessful even though the long protocol had been carried out (full term pregnancies had not resulted) and they were good responders whose total antral follicle number was over seven. The details of the 66 cases’ ovarian stimulation methods were: 52 cases of LA in which the first cycle was long protocol and the second cycle was antagonist protocol, seven cases of LAA, one case of LAAA, five cases of LLA and one case of LLAA. Regarding the ovulation induction method, an oral contraceptive was used for between 14 and 28 days from day 5 of menstruation in the cycle prior to extracting the eggs. For the long protocol, GnRH agonist was started two days before the finishing day of the oral contraceptive. When the number of ovarian follicles larger than 18mm increased to two, the type of ovulation induction drug was changed to hCG. In contrast, for the antagonist protocol, Doses of FSH at 150 ⬃ 300IU/ day were started from menstruation days 2 to 5 in the cycle of extracting eggs, and daily hypodermic injections of Cetrorelix 0.25 mg/day were started from the time the lead follicle reached 14 mm. When the average diameter of the lead ovarian follicle reached 20 mm the type of ovulation induction drug was changed to hCG. RESULTS: The FSH of the cycle prior to extraction of eggs was long protocol group 6.4⫾1.4, antagonist protocol group 6.5⫾1.5. Mean embryo transfer number was long protocol group 2.1⫾0.6, antagonist protocol group 2.2⫾0.5. The endometrial thickness at embryo transfer was long protocol group 12.3⫾2.3, and antagonist protocol group 12.0⫾2.7. No statistical differences were noted between the two groups for FSH of the cycle prior to extraction of eggs, mean embryo transfer number or endometrial thickness. However, we found a marked difference in the mean blastomere numbers on day 3, with the blastocyst formation rate being significantly higher in the antagonist protocol group. (Mean blastomere numbers: 6.7⫾2.1 vs 7.4⫾2.2, p⬍0.01, blastocyst formation rate: 33.2% vs 48.2%, p⬍0.01). The clinical pregnancy (FHM) rates were long protocol group 6.9% and antagonist protocol group 46.1%. Implantation rates were long protocol group 4.6% and antagonist protocol group 29.8%. The clinical pregnancy (FHM) rates and implantation rates were both significantly higher for the antagonist protocol group compared to the long protocol group (Clinical pregnancy rate and implantation rate: p⬍0.01). CONCLUSION: At this time our analysis of these results shows clearly that there were cases in which simply changing from the long method to the antagonist method brought success. In addition, it was proved in an actual case that GnRH agonist itself decreases embryo quality. Supported by: None. P-428
CONCLUSION: These results suggest that Follitropin alfa filled-bymass, (r-hFSH-fbm) is more effective than Follitropin alfa filled-by-bioassay for the ovarian stimulation of egg donor patients. The larger number of eggs and embryos obtained with r-hFSH-fbm although did not reach statistical significance, may be clinically relevant for recipients of donor eggs. Future prospective studies with a larger group of patients are needed to confirm our observations. Supported by: None
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Abstracts
Comparison of Pregnancy Rates in IVF Cycles Where Gonadotropin Releasing Hormone (GnRH) Antagonists Were Used to Suppress Luteinizing Hormone (LH) Surge in Place of GnRH Agonists. R. Madankumar, S. Brenner, D. Kenigsberg. Long Island Jewish Medical Center, New Hyde Park, NY; Long Island IVF, Port Jefferson, NY. OBJECTIVE: To maximize the pregnancy rates in IVF cycles, controlled ovarian hyperstimulation (COH) is produced utilizing injectable gonadotropins. COH is performed to increase the number of oocytes available for retrieval and subsequent insemination. Suppression of endogenous luteinizing hormone (LH) surge is necessary to properly time the retrieval. GnRH
Vol. 84, Suppl 1, September 2005