Table 1. Comparison of main outcome measures between luteal-phase and microdose GnRH-a protocols.
Variable Age at cycle start (mean ⫾ SEM) Number oocytes retrieved (mean ⫾ SEM) Number mature oocytes (mean ⫾ SEM) Percent mature oocytes retrieved (mean ⫾ SEM)
LUT (n ⫽ 19)
MICRO (n ⫽ 119)
28.3 ⫾ 0.68 16.2 ⫾ 1.6 10.1 ⫾ 1.2 61.4 ⫾ 4.1
33.9 ⫾ 0.37 16.8 ⫾ 0.83 11.5 ⫾ 0.59 69.1 ⫾ 1.6
Note: Differences between main outcome measures not significant by agematched ANOVA. Conclusions: A microdose follicular-phase GnRH-a ovarian stimulation protocol was equivalent to a luteal-phase GnRH-a protocol in total number of oocytes and number of mature oocytes retrieved. Microdose follicularphase GnRH-a ovarian stimulation protocols have the added patient benefits of lower cost and fewer days of injections. P-190 Recombinant human follicle stimulating hormone (r-hFSH) in patients referred to ovulation induction (OI): low dose step up versus step down protocols. J. Fernandez-Moris, C. Vin˜uela, V. Pizarro, J. Guerra. Unidad de Reproduccio´n Humana Hosp Gregorio Maran˜on, Madrid, Spain. Objective: To evaluate the ovarian response and the clinical outcomes obtained after the use of two different regimens of r-hFSH in those patients undergoing OI and intrauterine insemination (IUI) technique. Design: Prospective, randomized, comparative study. Materials/Methods: 136 patients (average age 33.2 ⫾ 3.7) were randomized to follow either a low dose (LD) or a step down (SD) regimen of OI with r-hFSH (Gonal-F®; Lab. Serono S.A., Madrid, Spain) subcutaneously. Most of the patients (n ⫽ 113, 90%) were affected by primary infertility. 179 cycles were performed; 155 cycles (87.6%) were followed by conjugal IUI, 12 cycles (6.7%) by donor IUI and 10 cycles (5.6%) by programmed coitus. In the LD treatment group, the ovarian stimulation was started on day 3 of the cycle with the administration of 75 IU/d of r-hFSH, with increases of 37.5 IU/d beginning on day 7 of treatment if no ovarian response (at least 1 follicle ⱖ 10 mm) was reached. In the SD treatment group, the stimulation was initiated with the administration of 150 IU/day of r-hFSH for 3 days (day 3-5 of the cycle) followed by a reduction to 75 IU on day 6 of the cycle. Follicular development was monitored on day 9 of the cycle by transvaginal sonography. Criteria for the hCG injection (10,000 IU, Profasi-HP®, Lab. Serono S.A., Madrid, Spain) was the presence of at least 1 follicle ⱖ18 mm. Natural micronized progesterone was used for luteal phase support. Results: The most relevant results are shown in Table 1. None cases of miscarriages or ovarian hyperstimulation were observed. Table 1. Low dose protocol No. cycles (no. patients) Age: mean ⫾ SD (range) Days of stimulation Ampoules administered (75 IU) No. follicles 10–16 mm No. follicles ⬎16 mm E2 day of hCG No. sonographic controls No. of pregnancies/cycle (%) No. of cancelled cycles (%)
86 (61) 32.8 ⫾ 3.5 (26–42)
Step-down protocol 93 (65) 33.5 ⫾ 3.8 (26–42)
8.8 ⫾ 1.8 9.2 ⫾ 2.4
7.8 ⫾ 2.1 10.8 ⫾ 2.3
1.5 ⫾ 1.6 1.3 ⫾ 1.2 292 ⫾ 344 1.3 ⫾ 0.5 16 (18.6)
1.6 ⫾ 1.5 1.5 ⫾ 0.9 324 ⫾ 612 1.2 ⫾ 0.5 10 (10.8)
3 (3.5)
4 (4.3)
P value N/A N.S. ⬍0.001 ⬍0.001 N.S. N.S. N.S. N.S. N.S. N.S.
Conclusions: Both regimens of r-hFSH (Gonal-F®) administration can be used in order to achieve an adequate follicular development. However, as a
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Abstracts
consequence of obtaining a similar follicular development, oestradiol serum level and patients clinical follow-up profiles, the significant difference in the number of ampoules required (p ⬍ 0.001) as well as the trend towards higher pregnancy rate showed in the group of patients treated with the low dose regimen make that this regimen can be considered as the preferential stimulation protocol in those patients referred to OI procedures.
P-191 The levels of serum vascular endothelial growth factor (VEGF) in women undergoing IVF/ET: a comparison with serum estradiol levels, correlated to IVF outcome. E. Levitas, M. Huleihel, E. Lunenfeld, S. Albotiano, I. Har-Vardi, G. Potashnik. Soroka Univ Medical Ctr, Faculty of Health Science, Ben-Gurion Univ of the Negev, Beer Sheva, Israel. Objective: Angiogenesis and granulosa cell proliferation are determinant factors in a successful follicular growth and development of mature oocytes, capable of fertilization and pregnancy. The aim of this study was to explore the value of serum VEGF during IVF cycles compared with serum estradiol concentrations (E2), follicle size and number, oocytes retrieved ,fertilization, implantation and pregnancy rates. Design: Prospective, descriptive study. Materials/Methods: The study included prospectively 18 patients undergoing the “long protocol” of ovarian stimulation for IVF for various infertility reasons: 9 couples with male related infertility, two women – pelvic adhesions and seven couples with unexplained infertility. Ovarian downregulation obtained using GnRH agonist and Controlled Ovarian Hyperstimulation (COH) achieved by daily administration of Gonadotropins according to an individually adjusted technique guided by serum estradiol levels and ovarian transvaginal sonography. Serum samples were obtained at various time points during COH starting the day of pituitary desensitization and ending 28 –30 days following embryo transfer (ET). The level of VEGF and estradiol were determined by using specific kits. Results: Mean age of women participated in the study was 26.9 years,mean early follicular FSH level—5.5 mIU/mL. Mean duration of gonadotropin treatment 13 days and mean number of ampules administered—33.5. Two weeks following GnRH agonist administration, the serum VEGF level was high (3068 ⫾ 3490 pg/mL) and inversely correlated to the E2 level (29 ⫾ 8.6 pg/mL). The serum VEGF level decreased gradually during the first 11 days of HMG treatment reaching a nadir (702 ⫾ 1982 pg/mL) during this time (p ⬍ 0.0006), while serum estradiol levels rose steadily. A second peak of VEGF serum levels (2697 ⫾ 2713 pg/mL, p ⬍ 0.002 compared with the nadir level) was positively correlated with the peak of E2 and follicle transition from a mean size of 14.1 to 15.3 mm. Following hCG injection and during the luteal phase the serum levels of VEGF remain high without a significant change respect to the peak level observed on the day of hCG administration. Three women included in the study became pregnant. We could not establish a correlation between VEGF levels and quantity or quality of oocytes, oocyte fertilization, pregnancy and implantation rates. Conclusions: In this prospective study we characterize the VEGF serum levels during IVF treatment according to the “long protocol”. We emphasize the presence of two VEGF peaks: one—following GnRH agonist treatment and the other one following the appearance of ovarian follicles above 14 mm in diameter. These findings might be correlated to the “flair effect” upon mid-luteal ovarian tissue for the first peak and growing presence of granulosa-theca cells accompanied by a process of angiogenesis for the second VEGF peak.
P-192 Ganirelix, a GnRH antagonist, significantly reduces IVF cancellation rates in ‘poor responders’. K. J. Elford, A. Leader. Univ of Ottawa, Ottawa, ON, Canada. Objective: To determine if women who were found to be poor responders in a previous IVF cycle had a lower cancellation rate in IVF cycles using Ganirelex (a GnRH antagonist) when compared to a standard Flare protocol using low dose Buserilin (a GnRH agonist). Design: Retrospective controlled trial looking at the cancellation rates in women (that had responded poorly in previous IVF attempts). In a subsequent cycle either Ganirelix or a standard Flare protocol was used. Age
Vol. 76, No. 3, Suppl. 1, September 2001