Diminishing Returns of Increasing Gonadotropin Dosage in Subsequent In Vitro Fertilization (IVF) Cycles?

Diminishing Returns of Increasing Gonadotropin Dosage in Subsequent In Vitro Fertilization (IVF) Cycles?

43% (40/93) of those in the recombinant FSH group (p⫽0.060). The rate of excessive response leading to cancellation was 2% (2/91) with HP-hMG and 8% (...

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43% (40/93) of those in the recombinant FSH group (p⫽0.060). The rate of excessive response leading to cancellation was 2% (2/91) with HP-hMG and 8% (7/93) with recombinant FSH. Endometrial thickness at the end of stimulation was similar in the HP-hMG (9.6 ⫾ 2.1 mm) and recombinant FSH (9.1 ⫾ 2.1 mm) groups. The ongoing pregnancy rate (viable fetus 12 ⫾ 2 weeks after hCG administration) as well as the live birth rate was 14% (13/91) in the HP-hMG group and 17% (16/93) in the recombinant FSH group. There were no multiple pregnancies in the HP-hMG group while 13% (2/16) of the pregnancies in the recombinant FSH group were twin pregnancies. The frequency of OHSS was 1% (1 mild) in the HP-hMG group and 3% (2 mild and 1 moderate) in the recombinant FSH group. The frequency of redness, pain, itching, swelling and bruising at the injection sites was comparable between treatment groups. CONCLUSION: Treatment with a highly purified menotropin preparation is associated with similar ovulation rates as recombinant FSH in anovulatory WHO Group II women failing to ovulate or conceive on clomiphene citrate. Supported by: Ferring Pharmaceuticals A/S, Copenhagen, Denmark.

OVARIAN STIMULATION-POOR RESPONDERS: ART P-481 Comparison of Microdose Flare-up and Antagonist Multiple Dose Protocols in Poor Responder Patients. A. Demirol, B. Girgin, T. Gurgan. CLINIC IVF Center, Ankara, Turkey; Hacettepe University Hospital, IVF Unit, Ankara, Turkey. OBJECTIVE: To compare the efficacy of two different regimens for poor responder patients in ICSI-ET cycles. DESIGN: Prospective-randomized study MATERIALS AND METHODS: Ninety patients with poor ovarian response in previous minimum two IVF cycles were randomized into two groups. All patients had two criteria for poor response; baseline FSH ⬎ 15 mIU/mL and less than four oocytes in all previous IVF attempts. The patients in Group I(microdose flare-up, n⫽45 patients) used low dose oral contraceptive (Desolett; Organon) with starting on day 1 of previous cycle for 21 days. On the third day of menstruation 40 ␮g.s.c/bid leuprolide acetate (Lucrin; Abbott) was started on day 2 followed by 450 IU/day human menopausal gonadotrophin(HMG) stimulation ( Menogon, Ferring) on day 3. The patients in Group II(antagonist multiple dose, n⫽45) received 450 IU/day HMG starting on day 3 and 0.25 mg cetrorelix administered daily when two or more follicles reached 13-14 mm diameter. HMG doses were adjusted according to the individual response and 10,000 IU HCG (Choragon, Ferring) was administered when et least two leading follicle reached 16 mm diameter. Oocyte retrieval was performed 36 h later than HCG, ICSI was performed for all patient and day 3 embryo transfer was preferred. RESULTS: Cycle outcomes are shown in Table I. There was no difference with respect to the cycle parameter. Implantation rate was significantly higher in Pregnancy rate was higher in microdose flare-up group but it did not reach the significant level.

CONCLUSION: Microdose flare-up protocol seems to have a better outcome in poor responder patients with significantly higher implantation rate. Supported by: We did not have any commercial support.

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P-482 Outcome of Minimal Stimulation IVF With Short-Term Application of GnRH Antagonist and Low Dose Gonadotropins in Natural Cycle and Cycle Using Clomiphene Citrate in Poor Responders. C. Hur, W. Lee, J. Lim. Maria Infertility Hospital, Seoul, Republic of Korea. OBJECTIVE: Minimal stimulation IVF has been offered to be a valuable alternative in poor responders. The objective of this study was to evaluate the efficacy of minimal stimulation IVF with GnRH antagonist and rFSH or HMG in cycle using clomiphene citrate in poor responders compared with that in natural cycle. DESIGN: Retrospective review of minimal stimulation cycle in natural and using clomiphene citrate in patients diagnosed as poor responders, previous low ovarian response in IVF cycles despite the high dose of gonadotropins, from January 2002 to December 2004. MATERIALS AND METHODS: A total of 125 patients underwent 180 cycles of minimal stimulation in natural cycles and 86 patients underwent 111 cycles using clomiphene citrate. GnRH antagonist 0.25mg (Cetrotide® ; Serono) and rFSH 150IU (Gonal F®; Serono) or HMG 150IU (IVF-M® ; LG Life Sciences) daily injections were started when the dominant follicle reached a diameter of at least 14mm in natural cycle, 16mm in cycle using clomiphene citrate, 100mg on days 3-7. GnRH antagonist was continued up to and including the day of ovulation triggering, gonadotropin was continued up to the day of ovulation triggering. When the dominant follicle reached a mean diameter of 17 to 20mm, 10,000IU of hCG were administered, and oocyte retrieval was performed 36 hours later. RESULTS: The mean age of the women was 37.2⫾4.9 for natural cycle and 38.1⫾5.0 for cycle using clomiphene citrate (P⫽.13, NS), the level of basal FSH was 11.2⫾6.3 and 11.4⫾5.2 (P⫽.87, NS). Cycle using clomiphene citrate had high rate of successful oocytes retrieval per attempt (58.3% and 87.4%, P⬍.05), more oocytes per pickup (1.0⫾0.2 and 1.9⫾1.3, P⬍.05), high rate of ET per cycle (42.8% and 77.5%, P⬍.05), more embryos transferred (1.0⫾0.2 and 1.6⫾0.7, P⬍.05). However endometrial thickness on the day of hCG injection was significantly thinner in clomiphene citrate cycle (9.5⫾2.0 and 8.1⫾1.5, P⬍.05). Clinical pregnancy rates per cycle and per ET were equivalent in both groups (7.2% and 9%, P⫽.58, 16.9% and 11.6%, P⫽.34). In cycle using clomiphene citrate, clinical PR was 23.3% when 2 or more embryos were transferred and 8.8% when only one embryo was transferred. But these differences were not statistically significant (P⫽.11). CONCLUSION: In poor responders, minimal stimulation protocol combined with GnRH antagonist can be a valuable alternative, especially in cycle using clomiphene citrate with more advantages than minimal stimulation in natural cycle. Supported by: None

P-483 Diminishing Returns of Increasing Gonadotropin Dosage in Subsequent In Vitro Fertilization (IVF) Cycles? E. Flisser, L. C. Krey, A. S. Berkeley. New York University School of Medicine, New York, NY. OBJECTIVE: IVF success is related to the number of mature oocytes retrieved. In some patients, despite high dose gonadotropin (Gn) stimulation, few oocytes are retrieved and few quality embryos are available for transfer. The goal of this study is to assess the result of increasing Gn dosage on subsequent IVF cycles. DESIGN: Retrospective analysis in a university-based IVF program. MATERIALS AND METHODS: We examined all patient IVF stimulation cycles from 7/1999 to 9/2004 selecting patients whose initial Gn dosing was 450 IU per day. From these patients we selected those that had initial 600 IU dosing per day in the following IVF cycle, regardless of the outcome of the first cycle. Gonadotropins used were Follicle Stimulating Hormone, Human Menopausal Gonadotropin, or a combination of the two. Patients selected were matched for the same type of cycle regimen in the subsequent stimulation: long protocol (n⫽4), microdose leuprolide acetate flare (microdose) (n⫽17) or Gonadotropin Releasing Hormone-antagonist (GnRHant) (n⫽40). All patients had variable Gn dosing after 4 days of stimulation according to the number of follicles observed on transvaginal ultrasound and the serum estradiol level. When indicated, GnRH-ant was initiated when the lead follicle was 13mm in mean diameter. Patients received 10,000 IU human chorionic gonadotrophin (hCG) intramuscularly when at

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least 2 follicles were ⱖ17mm in mean diameter; oocyte retrieval was performed ⬃36 h later. Cycles were compared for duration of stimulation and of GnRH-ant administration (when indicated); estradiol (E2) level (pg/mL) on day of hCG administration; number of 75IU ampoules used, of oocytes retrieved, and of 2-pronuclei embryos (2-PN) embryos created; and the E2/oocyte retrieved. Patients were categorized by type of stimulation cycle. Statistical significance (P⬍0.05) was determined by paired t-test, Wilcoxon Signed Rank Test, Fisher’s Exact Test and ␹2 test using SigmaStat©. RESULTS: The duration between cycles (mean days⫾SE) was: long protocol (336⫾126, range 128-689), microdose flare (307⫾76, range 57-1061), and GnRH-ant (186⫾25, range 30-742.) Although live birth rates were not significantly different for the long protocol (1/4 vs. 1/4, P⫽1.00) or microdose protocol (1/17 vs. 5/17, P⫽0.18), the live birth rate was significantly higher when 600IU was given with the GnRH-ant protocol (2/40 vs. 9/40, P⬍0.05).

CONCLUSION: There was a statistically significant difference in the number of oocytes retrieved and 2-PN embryos in the GnRH-ant cycles, and although small, they were clinically significant, since there was also a resulting significant difference in live births. Although no statistical difference was observed for the other protocols, this is likely to be related to the small sample size. Therefore, increasing the dosage of gonadotropins from 450IU to 600IU can increase the number of live births in patients who are low responders. Supported by: None.

P-484 Short Versus Long Gonadotropin Releasing Hormone Analogue Suppression Protocols for Superovulation in Intra Cytoplasm Sperm Injection Patients > 40 Years. M. Sbracia, A. Farina, R. Poverini, F. Morgia, M. Schimberni. CERM, Rome, Italy; BInstitute of Histology and Medical Embryology University of Bologna, Bologna, Italy; Bioroma, Rome, Italy. OBJECTIVE: The following study was conducted to determine in older patients which protocols of GnRH agonist suppression work better, long protocol or short protocol. DESIGN: We conducted a controlled randomized study in a single private IVF centre. MATERIALS AND METHODS: 220 women more than 39 years old undergoing IVF in our private Centre were selected for this study. The women, at their first IVF cycle, were randomized into two study groups using a computer generated number sequence: 110 cases were treated with a long protocol and 110 patients were treated with a short protocol for controlled ovarian hyperstimulation. The main outcome measure were: days of stimulation, E2 at the day of hCG, amount of FSH administered, number of oocytes collected, number of embryos obtained, pregnancy rate, implantation rate. RESULTS: Patients treated with a long protocol showed a significantly higher number of oocytes retrieved, number of embryos obtained and a higher pregnancy rate both for cycle and transfer with respect to the short

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Abstracts

protocol patients. The other parameter evaluated did not show any statistically significant differences. CONCLUSION: Our study showed that the long protocol performed better in older women than the short protocol. Our findings evidenced that the flare-up in older women may be detrimental. Supported by: None

P-485 Does the Addition of Letrozole in a GnRH Antagonist Protocol Offer Any Benefit in Low Response? A. Guille´n, A. Pacheco, A. Midsuf, S. Rabada´n, A. Requena, J. A. Garcı´a Velasco. Instituto Valenciano de Infertilidad, Madrid, Spain. OBJECTIVE: Low ovarian response in IVF is a major concern to the clinician. Letrozole, by increasing intraovarian androgens may enhance the expression of FSH receptor and thus, improve the ovarian response in COH. We evaluated the use of aromatase inhibitor, letrozole, as adjuvant treatment with a GnRH antagonist protocol in IVF patients with a previous long protocol canelled due to low response. DESIGN: The regimen started on day 2 of the cycle with 225 IU rFSH plus 150 IU hMG, and letrozole 2.5 mg/day during the first five days of stimulation. Daily antagonist was introduced when leading follicle reached 14 mm. MATERIALS AND METHODS: Sixty-seven IVF patients with a previous long protocol cancelled due to low response were included in this retrospective study in 2004. Patients were selected irrespective basal FSH and age, and stratified accordingly. RESULTS: According to age, 18 patients were under 34 years (31.4⫾1.97; FSH 10.57⫾5.78), 34 patients between 34-39 (36.73⫾1.97; FSH 9.54⫾3.96), 8 patients between 40-41 (40.37⫾0.51; FSH 11.98⫾4.8), and finally 7 patients were ⱖ42 (42.57⫾1.13;FSH 7.2⫾3.42). Respectively, cancellation rate due to no ovarian response or no embyo transfer was 44.4%, 29.4%, 75% and 57.1%; the number of retrieved oocytes were 5.7, 5.3, 6.0 and 6.3; and implantation/pregnancy rate 29.4/30%, 28.8/34.7%, 0/0% and 16.6/33.3%. According to FSH level, data were obtained for 64 patients. 36 patients had a basal FSH ⱕ10 ( FSH 6.76⫾2.02; Age 36.86⫾3.79), 11 patients had FSH between 10-12 (FSH 10.83⫾0.84, Age 34.9⫾3.36), and 17 patients had a basal FSH ⬎12 (FSH 15.94⫾3.68, Age 36.29⫾4.08). Respectively, cancellation rate due to no ovarian response or no embyo transfer was 33%,27.2% and 52.9%; the number of retrieved oocytes were 5.5, 5.6, and 5.1; and implantation/pregnancy rate 20.9/31.8%, 37.5/50% and 23.0/42.8%. CONCLUSION: Adding 2.5 mg of letrozole to high dose rFSH/hMG antagonist protocol offers an attractive alternative to patients with a previous cancelled IVF cycle due to low response. Age seems to be a more accurate predictive factor to low responders in pre-treatment counselling. Supported by: None

P-486 The Effect of the Length of the Follicular Phase on Pregnancy Outcome Following Single Embryo Transfer (ET) in Hypergonadotropic Women. B. Katsoff, A. Nazari, J. H. Check, C. Wilson, J. K. Choe, J. W. Krotec. UMDNJ, Robert Wood Johnson Med. School, Marlton, NJ. OBJECTIVE: Though women undergoing in vitro fertilization-embryo transfer (IVF-ET) with elevated day 3 serum FSH do not have a good pregnancy outcome following traditional controlled ovarian hyperstimulation (COH), they seem to do much better with minimal or no gonadotropin stimulation despite single ET. The aim of the present study was to determine the effect of the length of the follicular phase on pregnancy outcome in this group. DESIGN: Retrospective review. MATERIALS AND METHODS: A 7 year retrospective review was conducted on women with decreased egg reserve as manifested by elevated day 3 serum follicle stimulating hormone (FSH) levels, a decreased antral follicle count by sonography, and usually a previous history of poor response to gonadotropin stimulation. Oocyte retrievals were performed without any or with minimal stimulation with gonadotropins (maximum 600 IU per cycle). Only women aged ⱕ39 were included. The clinical (ultrasound

Vol. 84, Suppl 1, September 2005