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Achieving IVF-ET Pregnancy Rates in an Intrauterine Insemination Program With the Follistim Pen and Platelet-Activating Factor
P-254 A Study Comparing the Effects of Two Follicle-Stimulating Hormones used in Assisted Reproductive Technique. Y. Liu. Beijing Obstetrics and Gynecology Hospital, Beijing, China. OBJECTIVE: To compare the efficacy of recombinant follicle-stimulating hormone (rFSH) and highly-purified urinary follicle-stimulating hormone (uFSH HP) used in in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment. DESIGN: 76 patients undergoing in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment were divided into rFSH group (n⫽38) and uFSH HP group (n⫽38) randomly. MATERIALS AND METHODS: Two groups were used rFSH and uFSH HP respectively after the pituitaries were down regulated with Gonadotropin releasing hormone agonist (GnRH-a). Human chorionic gonadotrophin (HCG) were injected intramuscularly when the diameter of the dominant follicle were more than 18mm, and IVF/ICSI were treated after 36 hours of oocytes retrieval. The embryos were transferred 2 days later. The results were observed including the number of ampoules, follicles and oocytes retrieved, serum estradiol level, the fertilization rate, the pregnancy rates and the rate of complications. RESULTS: There were significant difference in the number of ampoules between rFSH group (34.50⫾7.87) and uFSH HP group (40.47⫾9.22) (P⬍0.05). The total doses of rFSH group was lower than those of uFSH HP group [2587.50⫾590.23IU vs. 3035.53⫾691.30IU (P⬍0.05)]. There were no significant difference in the number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, and number of oocytes retrieved. The fertilization rate was higher in rFSH group(87.18%) than in uFSH HP (73.65%)( P⬍0.05). The pregnancy rates were 36.8% and 26.3% for each group respectively. No differences were found in the number of spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), and the weeks and the weights of the infants(P⬎.05). CONCLUSIONS: rFSH produced higher fertilization rate and pregnancy rate than uFSH, and the total dose required was lower. It was a more efficiency and save follicle stimulating hormone, and more suitable for clinical application. Supported by: None
P-255 X-Chromosome Inactivation (XCI) in Newborns Conceived Through Intracytoplasmic Sperm Injection (ICSI). C. Hatakeyama, M. Penaherrera, W. Robinson, S. Ma. University of British Columbia, Vancouver, BC, Canada. OBJECTIVE: Non-random (skewed) XCI, defined as the preferential inactivation of one of the two X chromosomes in females, has been associated with the physiological selection of “healthy” cells in incidences of mosaicism. We hypothesize that XCI pattern is more non-random in the ICSI newborns because they might have developed from embryos with reduced precursor pools due to a combination of ICSI-related risk factors such as the higher rate of chromosomal abnormalities in the sperm, advanced maternal age, and the invasiveness of the procedure. We propose to use XCI as an indirect assessment of possible incidences of mosaicism (i.e. chromosomal abnormalities in some but not all cells) in ICSI conceptions and compare the pattern of XCI in ICSI newborns to that in the general population. DESIGN: A prospective study. MATERIALS AND METHODS: A methylation-based XCI assay was performed on DNA extracted from cord blood from 44 female ICSI newborns with normal karyotypes and 74 female controls (aged 0-19 years). The XCI assay involves methylation-sensitive restriction enzyme digestion followed by PCR amplification of the differentially methylated CpG sites of the X-linked Androgen Receptor gene. Fisher’s exact test will also be used to statistically detect a difference in the rates of skewed XCI in each group. RESULTS: The mean degree of skewing of XCI was 66.3% and 69.8% for ICSI and control, respectively. An extremely skewed XCI pattern (⬎ 90% skewed) was observed in 5.1% of the ICSI group and 10.8% in the control group, which is not statistically significant (P⬎0.5). CONCLUSIONS: No significant difference was found in XCI patterns between ICSI newborns and controls primarily because our data was pre-
FERTILITY & STERILITY威
liminary and sample size was insufficient. Although there may indeed be no difference between ICSI and naturally conceptions, further study needs to be done to confirm this. Supported by: This study was supported by the Hospital for Sick Children’s Foundation (to SM) and the Canadian Institute for Health Research (to WPR)
P-256 Achieving IVF-ET Pregnancy Rates in an Intrauterine Insemination Program With the Follistim Pen and Platelet-Activating Factor. W. E. Roudebush, D. B. Shapiro, S. Barrick. Reproductive Biology Associates, Atlanta, GA. OBJECTIVE: Intrauterine insemination (IUI) remains the first line of treatment for infertile patients. While IVF-ET rates are higher (40-45% nationally; ⬍35 years old; CDC ART-2002) it is typically not affordable for all patients. Therefore, many patients do not seek treatment. Improving IUI pregnancy rates may recruit these “lost” patients. The Follistim Pen along with the Follistim AQ Cartridge (Organon Pharmaceuticals USA Inc., Roseland, NJ) is a novel recombinant gonadotropin (follitropin beta, Organon) delivery system that results in better patient compliance and potentially provides lower dose (daily and overall) requirements, thus reducing costs. Improved IUI rates have been observed with use of the Follistim Pen. Platelet-activating factor (PAF), a unique signaling phospholipid that enhances sperm motility, has also been demonstrated to independently increase IUI per cycle pregnancy rates. The study objective was to determine IUI per cycle pregnancy rates between the Follistim Pen and the injectable form of Follistim for ovulation induction with both utilizing PAF sperm washing. DESIGN: Retrospective analysis of 89 IUI patient (female age ⱕ35 years; no down regulation; no male factor) cycles undergoing ovulation induction by the injectable form of Follistim (Follistim Injectable; control) or the Follistim Pen with PAF sperm washing. MATERIALS AND METHODS: Ovarian cycle stimulation (OI) was controlled by the recombinant gonadotropin follitropin beta (Follistim Pen or Follistim injectable). Stimulations were started on cycle day 3 with 75-225 IU daily (with dosages individually titrated based upon patient age and previous response). Frequent ultrasound monitoring with estradiol (E2) observation was performed until the lead follicle was at least 18mm in all but exceptional cases. IUI was performed 12-18 hours and again in 36 to 38 hours following hCG injection. Silica particle suspension (PureCeption, SAGE-Cooper Surgical, Trumbull, CT) washed sperm were exposed to an exogenous mixture of PAF (10-7M) in sperm wash medium (Quinn’s, SAGE-Cooper Surgical). Following a 15-minute exposure period, sperm were washed free of PAF. Pregnancy outcome (indicated by presence of a beating fetal heart) was recorded for each group. Data was subjected to Chi-squared analysis and Student’s t-test. RESULTS: Patients receiving the Follistim Pen (17/36; 47.2%) had a significantly (2⫽3.98; P⬍0.05) higher per cycle pregnancy than patients receiving Follistim Injectable (13/53; 24.5%) during OI-IUI therapy. Multiple rates were also observed to have no significant difference (Follistim Injectable, 30.8%); Follistim Pen, 29.4%). CONCLUSIONS: The use of the Follistim Pen combined with the PAF sperm wash procedure significantly improves IUI pregnancy rates. This study confirms the original independent studies demonstrating the effectiveness of the Follistim Pen and sperm washing with PAF in an IUI program. By optimizing patient compliance and gonadotropin delivery efficiency along with enhancing sperm motility performance IUI pregnancy rates can now compete with IVF-ET. This will permit patients, who normally would not seek infertility treatment, the opportunity to achieve parenthood. Supported by: Supported, in part, by an unrestricted grant from OrganonUSA.
P-257 Stimulation Length, Number of High-Sized Follicles and Estradiol on the hCG Injection Day Are Multiple Pregnancy Risk Factors in IUI. M. A. Melo, M. Meseguer, C. Simon, A. Pellicer, J. Remohi, N. Garrido. Instituto Universitario IVI, Valencia, Spain.
S241
P-255 X-Chromosome Inactivation (XCI) in Newborns Conceived Through Intracytoplasmic Sperm Injection (ICSI). C. Hatakeyama, M. Penaherrera, W. Robinson, S. Ma. University of British Columbia, Vancouver, BC, Canada. OBJECTIVE: Non-random (skewed) XCI, defined as the preferential inactivation of one of the two X chromosomes in females, has been associated with the physiological selection of “healthy” cells in incidences of mosaicism. We hypothesize that XCI pattern is more non-random in the ICSI newborns because they might have developed from embryos with reduced precursor pools due to a combination of ICSI-related risk factors such as the higher rate of chromosomal abnormalities in the sperm, advanced maternal age, and the invasiveness of the procedure. We propose to use XCI as an indirect assessment of possible incidences of mosaicism (i.e. chromosomal abnormalities in some but not all cells) in ICSI conceptions and compare the pattern of XCI in ICSI newborns to that in the general population. DESIGN: A prospective study. MATERIALS AND METHODS: A methylation-based XCI assay was performed on DNA extracted from cord blood from 44 female ICSI newborns with normal karyotypes and 74 female controls (aged 0-19 years). The XCI assay involves methylation-sensitive restriction enzyme digestion followed by PCR amplification of the differentially methylated CpG sites of the X-linked Androgen Receptor gene. Fisher’s exact test will also be used to statistically detect a difference in the rates of skewed XCI in each group. RESULTS: The mean degree of skewing of XCI was 66.3% and 69.8% for ICSI and control, respectively. An extremely skewed XCI pattern (⬎ 90% skewed) was observed in 5.1% of the ICSI group and 10.8% in the control group, which is not statistically significant (P⬎0.5). CONCLUSIONS: No significant difference was found in XCI patterns between ICSI newborns and controls primarily because our data was pre-
FERTILITY & STERILITY威
liminary and sample size was insufficient. Although there may indeed be no difference between ICSI and naturally conceptions, further study needs to be done to confirm this. Supported by: This study was supported by the Hospital for Sick Children’s Foundation (to SM) and the Canadian Institute for Health Research (to WPR)
P-256 Achieving IVF-ET Pregnancy Rates in an Intrauterine Insemination Program With the Follistim Pen and Platelet-Activating Factor. W. E. Roudebush, D. B. Shapiro, S. Barrick. Reproductive Biology Associates, Atlanta, GA. OBJECTIVE: Intrauterine insemination (IUI) remains the first line of treatment for infertile patients. While IVF-ET rates are higher (40-45% nationally; ⬍35 years old; CDC ART-2002) it is typically not affordable for all patients. Therefore, many patients do not seek treatment. Improving IUI pregnancy rates may recruit these “lost” patients. The Follistim Pen along with the Follistim AQ Cartridge (Organon Pharmaceuticals USA Inc., Roseland, NJ) is a novel recombinant gonadotropin (follitropin beta, Organon) delivery system that results in better patient compliance and potentially provides lower dose (daily and overall) requirements, thus reducing costs. Improved IUI rates have been observed with use of the Follistim Pen. Platelet-activating factor (PAF), a unique signaling phospholipid that enhances sperm motility, has also been demonstrated to independently increase IUI per cycle pregnancy rates. The study objective was to determine IUI per cycle pregnancy rates between the Follistim Pen and the injectable form of Follistim for ovulation induction with both utilizing PAF sperm washing. DESIGN: Retrospective analysis of 89 IUI patient (female age ⱕ35 years; no down regulation; no male factor) cycles undergoing ovulation induction by the injectable form of Follistim (Follistim Injectable; control) or the Follistim Pen with PAF sperm washing. MATERIALS AND METHODS: Ovarian cycle stimulation (OI) was controlled by the recombinant gonadotropin follitropin beta (Follistim Pen or Follistim injectable). Stimulations were started on cycle day 3 with 75-225 IU daily (with dosages individually titrated based upon patient age and previous response). Frequent ultrasound monitoring with estradiol (E2) observation was performed until the lead follicle was at least 18mm in all but exceptional cases. IUI was performed 12-18 hours and again in 36 to 38 hours following hCG injection. Silica particle suspension (PureCeption, SAGE-Cooper Surgical, Trumbull, CT) washed sperm were exposed to an exogenous mixture of PAF (10-7M) in sperm wash medium (Quinn’s, SAGE-Cooper Surgical). Following a 15-minute exposure period, sperm were washed free of PAF. Pregnancy outcome (indicated by presence of a beating fetal heart) was recorded for each group. Data was subjected to Chi-squared analysis and Student’s t-test. RESULTS: Patients receiving the Follistim Pen (17/36; 47.2%) had a significantly (2⫽3.98; P⬍0.05) higher per cycle pregnancy than patients receiving Follistim Injectable (13/53; 24.5%) during OI-IUI therapy. Multiple rates were also observed to have no significant difference (Follistim Injectable, 30.8%); Follistim Pen, 29.4%). CONCLUSIONS: The use of the Follistim Pen combined with the PAF sperm wash procedure significantly improves IUI pregnancy rates. This study confirms the original independent studies demonstrating the effectiveness of the Follistim Pen and sperm washing with PAF in an IUI program. By optimizing patient compliance and gonadotropin delivery efficiency along with enhancing sperm motility performance IUI pregnancy rates can now compete with IVF-ET. This will permit patients, who normally would not seek infertility treatment, the opportunity to achieve parenthood. Supported by: Supported, in part, by an unrestricted grant from OrganonUSA.
P-257 Stimulation Length, Number of High-Sized Follicles and Estradiol on the hCG Injection Day Are Multiple Pregnancy Risk Factors in IUI. M. A. Melo, M. Meseguer, C. Simon, A. Pellicer, J. Remohi, N. Garrido. Instituto Universitario IVI, Valencia, Spain.
S241