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Clinical outcome of intracytoplasmic sperm injection (ICSI) with frozen-thawed epididymal and testicular sperm with an investigation of chromosomal abnormalities in the sperm and ICSI pregnancies
Monday, October 18, 2004 5:15 P.M. O-116 Live births after IVF in men with a DNA fragmentation index of 30% or greater as determined by the Sperm Chromatin Structure Assay (SCSA™). F. Barnes, F. Rabara, A. Murphy, C. Zouves. Zouves Fertility Center, Daly City, CA. OBJECTIVE: Evaluate the implantation and birth frequency in couples where the male partner had a DFI of ⱖ 30 %. DESIGN: Retrospective review of IVF cycles with a DNA fragmentation index (DFI) ⱖ 30%. MATERIALS AND METHODS: Semen samples provided by men undergoing IVF were subjected to SCSA™ testing within 0 –180 days of IVF. Samples were produced by masturbation into specimen cups (Mckesson Medi-pak #37–2469P) and processed within 15–300 minutes. Samples were evaluated for count and motility and frozen neat and stored for one to fourteen days in liquid nitrogen Dewars. Frozen samples were sent to SCSA™ Diagnostics, Inc, Brookings, SD for testing. Results were available within 7 days. Men with a high DFI (ⱖ 30%) were advised to use Fertility Blend™ supplement for men and couples were counseled to add an additional embryo to the transfer if available. In vitro fertilization (IVF), embryo culture and embryo transfer were performed by processes standard to the industry. Sperm donation was not suggested as an option for IVF treatment. Data presented includes men with DFI’s ⱖ 30%, pregnancy and birth data where derived from only the first cycle following SCSA testing. Data is grouped in thirty-day intervals from SCSA testing to egg recovery. RESULTS: Men with high DFI’s were consistently able to produce healthy children following in vitro fertilization regardless of the time of testing to egg retrieval.
OBJECTIVE: The Sperm Chromatin Structure Assay (SCSA), a newly available diagnostic tool for IVF practitioners, measures the percentage of sperm with high levels of DNA fragmentation ⫺ DNA Fragmentation Index (% DFI). The results are used to ascertain the fertility potential of patients receiving fertility treatment. The objective of this study was to evaluate the correlation between DFI and outcome in patients receiving ICSI treatment. DESIGN: A retrospective analysis of 68 IVF patient cycles, between January 2003 and April 2004 with SCSA test results. MATERIALS AND METHODS: Patients were included if they received ICSI, a day 3 transfer and did not have pre-implantation genetic diagnosis. Patients were divided into 3 groups depending on DFI score: * Excellent fertility potential ⬃ ⫺/⬍15% DFI (Group I) * Good fertility potential ⫺/⬍ 15–30% DFI (Group II) * Poor fertility potential ⬃ ⬎30% DFI (Group III) The embryos were scored on day 3 accounting for morphology, cell number, and cell fragmentation, using a grading system whereby 4 is highest quality and 1 is poorest quality. A statistical analysis using one-way ANOVA and CHI-SQUARED test was used to determine any significant trends in rates of fertilization, embryo quality and pregnancy (⫹hCG) with a P level of 0.05. RESULTS: Of the total population, 19 patients were in group I, 29 in group II and 20 in group III. Fertilization rates in groups I, II and III were 62.2 (⫾18.7), 60.9 (⫾20.8) and 50.7 (⫾20.7) respectively (P⬎0.05). Average embryo quality on day 3 in groups I, II and III was 2.83 (⫾0.82), 2.97 (⫾0.59) and 2.98 (⫾0.58) respectively (P⬎0.05). Pregnancy rates in groups I, II and III were 10/19 (53%), 16/29 (55%) and 9/20 (45%) respectively (P⬎0.05). The difference in female age between the 3 groups was not significant; the average age in groups I, II and III was 34.2 (⫾5.46), 33.9 (⫾4.75) and 33.95 (⫾4.40) respectively (P⬎0.05). The number of embryos transferred between the 3 groups was not significant; the average number transferred in groups I, II and III was 2.74 (⫾0.93), 2.48 (⫾0.87) and 3.25 (⫾1.773) respectively (P⬎0.05). CONCLUSION: This analysis of initial data shows no significant difference between all groups in fertilization rate (although there does seem to be a trend towards decreasing fertilization rate with increasing DFI), embryo quality on day 3 or pregnancy rate. An extension of the present study may be warrented to strengthen the value of these findings by increasing the size of the study groups, and improving standards of protocol, for example performing the SCSA analysis on the day of oocytes retrieval, removing time factors and effects of any treatment (such as anti-oxidant therapy). Most importantly, these results do show that even with a high DFI score, patients can still achieve a pregnancy, including one patient with a DFI of 49 who has an ongoing twin pregnancy. Supported by: None
Monday, October 18, 2004 5:45 P.M. O-118
1: Clinical pregnancy defined as the presence of a fetal sac at 6 weeks. 2: Sacs electively terminated prior to birth. Added note: three patients with DFI’s ⱖ50%, within 4 and 59 days of egg retrieval produced 7 healthy children following IVF. CONCLUSION: The data presented is in contrast to reports that a DFI ⱖ 30% strongly predicts a male patient’s inability to produce a sustained pregnancy. Fertility Blend™ supplement for men contains L-Carnitine and other antioxidants that may have led to reduced and improved DFI scores by the time of IVF. Men with an initial DFI ⱖ 30% should not move immediately to sperm donation when attempting to father a child by IVF. Supported by: None
Monday, October 18, 2004 5:30 P.M. O-117 A high DFI score does not preclude patients from achieving a pregnancy with ICSI. T. A. Elliott, T. H. Taylor, C. A. Jacobs, W. E. Roudebush, W. Brockman, Z. P. Nagy. Reproductive Biology Associates, Atlanta, GA.
FERTILITY & STERILITY威
Clinical outcome of intracytoplasmic sperm injection (ICSI) with frozen-thawed epididymal and testicular sperm with an investigation of chromosomal abnormalities in the sperm and ICSI pregnancies. S. Ma, H. Gao, S. S. Tang, B. Ho Yuen, V. Chow, M. Nigro. University of British Columbia, Vancouver, BC, Canada. OBJECTIVE: The aims of the study are: 1) to measure the efficacy of ICSI, in terms of clinical outcome, with frozen-thawed epididymal and testicular spermatozoa, 2) to correlate chromosomal abnormalities in the frozen-thawed spermatozoa with the clinical outcome, and 3) to investigate cytogenetically the newborn babies conceived from this procedure. DESIGN: Prospective study MATERIALS AND METHODS: In 31 patients (17 suffering from obstructive azoospermia, OA, 9 from non-obstructive azoospermia, NOA, 5 from failed microsurgical reversal for vasectomy), sperm were retrieved from either microsurgical epididymal sperm aspiration (MESA) (n⫽20) or testicular biopsies (TESE) (n⫽11). Cryopreserved spermatozoa from the day of operation were frozen-thawed and used for 41 planned ICSI cycles. Spermatozoa leftover from 10 ICSI procedures (5 from MESA and 5 from TESE) were processed for FISH, after patients’ consent. Probes for chromosomes X, Y and 18 were used to detect chromosomal abnormalities in the patient sperm, as well as in sperm from 5 proven fertile men (controls). Chromosomal analysis of cord blood from newborn babies was also carried out. RESULTS: Fertilization rates were similar in MESA and TESE groups
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(77% vs. 73%). At least two embryos were replaced in all planned ICSI cycles with frozen-thawed spermatozoa. Pregnancy rates were 38.5% and 46.7%, respectively in MESA and TESE groups. Patients who suffered from NOA had lower pregnancy rates than the combined rates of the other groups (12.5% vs. 48.5%, P⬍0.05). A total of 50517 sperm in OA, 2162 sperm in NOA and 50582 sperm in control were examined. Disomy for sex chromosomes in both the infertile groups were significantly higher than that in the control group (0.59 vs. 0.38; 2.54 vs. 0.38, P⬍ 0.0001). Furthermore, the rate of disomy for chromosome 18 and sex chromosomes from NOA was also significantly higher than those from OA (1.02 vs. 0.16; 2.54 vs. 0.59, P⬍0.0001). Only two miscarriages occurred in OA, and one had an abnormal karyotype (45,XY,-21). 14 out of 20 newborn babies were studied cytogenetically and one case (7%) from OA and TESE showed a sex reversal karyotype (a male infant with 46,XX). CONCLUSION: Frozen-thawed spermatozoa from various types of azoospermia can be used efficiently in planned ICSI cycles. ICSI fertilization and pregnancy rates of these spermatozoa were comparable to those from ejaculated samples. Elevated chromosomal abnormalities in the sperm from NOA may be associated with low pregnancy rates and a large sample size is needed to confirm this hypothesis. Further investigation is needed to determine whether the rate of sex reversal in newborn babies from ICSI is higher than those from the normal population, that our finding is related to the source of sperm used for ICSI, or that this is simply a sporadic event. Supported by: This study is supported by CIHR and the Hospital for Sick Children Foundation.
OTHER: ART Monday, October 18, 2004 2:00 P.M. O-119 Birth weight of singletons born after modified natural cycle IVF compared with singletons born after IVF with ovarian hyperstimulation. M. Keizer, K. Middelburg, N. Vogel, M. J. Pelinck, A. Simons, A. Hoek. University Hospital Groningen, Groningen, Netherlands. OBJECTIVE: The birth weight of singleton children resulting from IVF with controlled ovarian hyperstimulation (COH-IVF), is lower than the birth weight of singletons resulting from spontaneous conceptions. It is hypothesized that this is caused by either ovarian hyperstimulation, IVF laboratory procedures or patient selection. In the present study, birth weights of singletons born after modified natural cycle IVF, in which no ovarian hyperstimulation is performed, were compared to singletons resulting from COH-IVF. DESIGN: Two cohorts were formed. The first cohort consisted of 61 singletons, born between November 2001 and December 2003, all resulting from modified natural cycle IVF. The second cohort consisted of 583 singletons, born between December 1988 and December 2003, all resulting from COH-IVF. Duration of pregnancy and birth weights were compared between cohorts. MATERIALS AND METHODS: For modified natural cycle IVF, the one (or two) oocyte(s) that naturally reaches dominance was used for IVF. No ovarian hyperstimulation was applied. The GnRH-antagonist cetrorelix was administered to prevent untimely LH-surges. In the majority of cases, one single embryo was available for transfer. For COH-IVF, a downregulation or flare-up protocol was used, aiming at about ten oocytes and transfer of two or three embryos. RESULTS: Results are shown in the table.
Patient age, parity and duration of pregnancy were not different between groups. Birth weights were significantly (P ⫽ 0.003) larger in the modified natural cycle IVF group compared to the COH-IVF group. CONCLUSION: Singletons born after modified natural cycle have significantly larger birth weights compared to singletons resulting from COHIVF. Since the laboratory procedure is equal in both groups, we hypothesize that this difference is caused by lack of ovarian hyperstimulation. However, patient selection can not be excluded. Supported by: This study was supported by a grant from the University Hospital Groningen and from Zon-Mw, the Netherlands.
Monday, October 18, 2004 2:15 P.M. O-120 Early evidence of efficacy and safety for a novel sustained-release recombinant human follicle stimulating hormone (FSH-SR). T. Mathews, L. M. Gibbons, A. Priestley, S. Woods, D. W. Warne, L. O’Dea. Bourn Hall Clinic, Cambridge, United Kingdom; Serono International SA, Geneva, Switzerland; Serono, Inc., Rockland, MA. OBJECTIVE: Recombinant hFSH is widely utilized for induction of ovulation in oligo-anovulatory infertility and for stimulation of multiple follicular development in ART. Over the course of a stimulation cycle and depending on the treatment protocol, a patient may self-inject more than 40 times, and have to repeat the process over a number of cycles. A sustainedrelease (SR) preparation of r-hFSH (follitropin alfa for injection) would offer advantages to the patient, nurse and physician ⫺ fewer injections, improved compliance, and a reduced potential for medication errors. FSH-SR was developed in conjunction with Alkermes, Cambridge, MA, USA using follitropin alfa and Alkermes’ patented ProLease® technology. The present study was performed to assess the suitability of this novel formulation of FSH-SR for ovarian stimulation through the monitoring of safety and pharmacodynamic markers (follicle growth and estradiol [E2] production) following its administration to healthy women volunteers. DESIGN: Prospective, open-label, single-center IRB approved study. MATERIALS AND METHODS: 36 healthy, normally-cycling women with normal baseline reproductive hormone values were enrolled. Subjects were treated in sequential groups of 4 with a single dose of FSH-SR administered SC. Five groups (n⫽20) were down-regulated with a GnRH analogue, goserelin acetate, and 4 groups (n⫽16) were studied in spontaneous cycles. Based on a prospectively defined algorithm, the dose of each group was chosen by a Study Steering Committee. Serum FSH, follicular response as assessed by ultrasound, and serum E2 were assessed at baseline and for 49 days after injection. Safety assessments were performed on each patient visit. The main outcome measure was follicle growth as assessed by the number and size of follicles, and serum E2 over time. RESULTS: Following the dosing algorithm, downregulated subjects were administered single doses of 146 mcg, 73 mcg, 218 mcg (x2) and 328 mcg in groups of 4. Non-downregulated subjects were administered 146 mcg, 218 mcg, 73 mcg and 36 mcg. All dose groups showed evidence of FSH effect with a rise in serum E2 and follicular growth. Higher doses were associated with pre-ovulatory E2 values (⬎3500 pmol/mL), with follicles of 20 mm diameter and up to 24 responding follicles (⬎11 mm). Duration of effect, as assessed by days of rising E2 values, was also dose-dependent and up to 10 days (median 4 –9 days). Down-regulation was associated with slower increases in serum E2 and follicle number. FSH-SR was welltolerated in the doses administered, generally and locally, by the study subjects. There were no serious adverse events. CONCLUSION: A FSH-SR dose-dependent effect is identified on follicular development and E2 production. Pre-ovulatory E2 levels and mature follicle development are achieved with a single dose of FSH-SR. FSH-SR was well tolerated by volunteers and may offer a novel option as initial treatment in both OI and ART. Supported by: Serono
Monday, October 18, 2004 2:30 P.M. O-121 Genomic and proteomic analyses of the endometrium during the window of implantation following laser capture microdissection: Compar-
S48
Abstracts
Vol. 82, Suppl. 2, September 2004
OBJECTIVE: The Sperm Chromatin Structure Assay (SCSA), a newly available diagnostic tool for IVF practitioners, measures the percentage of sperm with high levels of DNA fragmentation ⫺ DNA Fragmentation Index (% DFI). The results are used to ascertain the fertility potential of patients receiving fertility treatment. The objective of this study was to evaluate the correlation between DFI and outcome in patients receiving ICSI treatment. DESIGN: A retrospective analysis of 68 IVF patient cycles, between January 2003 and April 2004 with SCSA test results. MATERIALS AND METHODS: Patients were included if they received ICSI, a day 3 transfer and did not have pre-implantation genetic diagnosis. Patients were divided into 3 groups depending on DFI score: * Excellent fertility potential ⬃ ⫺/⬍15% DFI (Group I) * Good fertility potential ⫺/⬍ 15–30% DFI (Group II) * Poor fertility potential ⬃ ⬎30% DFI (Group III) The embryos were scored on day 3 accounting for morphology, cell number, and cell fragmentation, using a grading system whereby 4 is highest quality and 1 is poorest quality. A statistical analysis using one-way ANOVA and CHI-SQUARED test was used to determine any significant trends in rates of fertilization, embryo quality and pregnancy (⫹hCG) with a P level of 0.05. RESULTS: Of the total population, 19 patients were in group I, 29 in group II and 20 in group III. Fertilization rates in groups I, II and III were 62.2 (⫾18.7), 60.9 (⫾20.8) and 50.7 (⫾20.7) respectively (P⬎0.05). Average embryo quality on day 3 in groups I, II and III was 2.83 (⫾0.82), 2.97 (⫾0.59) and 2.98 (⫾0.58) respectively (P⬎0.05). Pregnancy rates in groups I, II and III were 10/19 (53%), 16/29 (55%) and 9/20 (45%) respectively (P⬎0.05). The difference in female age between the 3 groups was not significant; the average age in groups I, II and III was 34.2 (⫾5.46), 33.9 (⫾4.75) and 33.95 (⫾4.40) respectively (P⬎0.05). The number of embryos transferred between the 3 groups was not significant; the average number transferred in groups I, II and III was 2.74 (⫾0.93), 2.48 (⫾0.87) and 3.25 (⫾1.773) respectively (P⬎0.05). CONCLUSION: This analysis of initial data shows no significant difference between all groups in fertilization rate (although there does seem to be a trend towards decreasing fertilization rate with increasing DFI), embryo quality on day 3 or pregnancy rate. An extension of the present study may be warrented to strengthen the value of these findings by increasing the size of the study groups, and improving standards of protocol, for example performing the SCSA analysis on the day of oocytes retrieval, removing time factors and effects of any treatment (such as anti-oxidant therapy). Most importantly, these results do show that even with a high DFI score, patients can still achieve a pregnancy, including one patient with a DFI of 49 who has an ongoing twin pregnancy. Supported by: None
Monday, October 18, 2004 5:45 P.M. O-118
1: Clinical pregnancy defined as the presence of a fetal sac at 6 weeks. 2: Sacs electively terminated prior to birth. Added note: three patients with DFI’s ⱖ50%, within 4 and 59 days of egg retrieval produced 7 healthy children following IVF. CONCLUSION: The data presented is in contrast to reports that a DFI ⱖ 30% strongly predicts a male patient’s inability to produce a sustained pregnancy. Fertility Blend™ supplement for men contains L-Carnitine and other antioxidants that may have led to reduced and improved DFI scores by the time of IVF. Men with an initial DFI ⱖ 30% should not move immediately to sperm donation when attempting to father a child by IVF. Supported by: None
Monday, October 18, 2004 5:30 P.M. O-117 A high DFI score does not preclude patients from achieving a pregnancy with ICSI. T. A. Elliott, T. H. Taylor, C. A. Jacobs, W. E. Roudebush, W. Brockman, Z. P. Nagy. Reproductive Biology Associates, Atlanta, GA.
FERTILITY & STERILITY威
Clinical outcome of intracytoplasmic sperm injection (ICSI) with frozen-thawed epididymal and testicular sperm with an investigation of chromosomal abnormalities in the sperm and ICSI pregnancies. S. Ma, H. Gao, S. S. Tang, B. Ho Yuen, V. Chow, M. Nigro. University of British Columbia, Vancouver, BC, Canada. OBJECTIVE: The aims of the study are: 1) to measure the efficacy of ICSI, in terms of clinical outcome, with frozen-thawed epididymal and testicular spermatozoa, 2) to correlate chromosomal abnormalities in the frozen-thawed spermatozoa with the clinical outcome, and 3) to investigate cytogenetically the newborn babies conceived from this procedure. DESIGN: Prospective study MATERIALS AND METHODS: In 31 patients (17 suffering from obstructive azoospermia, OA, 9 from non-obstructive azoospermia, NOA, 5 from failed microsurgical reversal for vasectomy), sperm were retrieved from either microsurgical epididymal sperm aspiration (MESA) (n⫽20) or testicular biopsies (TESE) (n⫽11). Cryopreserved spermatozoa from the day of operation were frozen-thawed and used for 41 planned ICSI cycles. Spermatozoa leftover from 10 ICSI procedures (5 from MESA and 5 from TESE) were processed for FISH, after patients’ consent. Probes for chromosomes X, Y and 18 were used to detect chromosomal abnormalities in the patient sperm, as well as in sperm from 5 proven fertile men (controls). Chromosomal analysis of cord blood from newborn babies was also carried out. RESULTS: Fertilization rates were similar in MESA and TESE groups
S47
(77% vs. 73%). At least two embryos were replaced in all planned ICSI cycles with frozen-thawed spermatozoa. Pregnancy rates were 38.5% and 46.7%, respectively in MESA and TESE groups. Patients who suffered from NOA had lower pregnancy rates than the combined rates of the other groups (12.5% vs. 48.5%, P⬍0.05). A total of 50517 sperm in OA, 2162 sperm in NOA and 50582 sperm in control were examined. Disomy for sex chromosomes in both the infertile groups were significantly higher than that in the control group (0.59 vs. 0.38; 2.54 vs. 0.38, P⬍ 0.0001). Furthermore, the rate of disomy for chromosome 18 and sex chromosomes from NOA was also significantly higher than those from OA (1.02 vs. 0.16; 2.54 vs. 0.59, P⬍0.0001). Only two miscarriages occurred in OA, and one had an abnormal karyotype (45,XY,-21). 14 out of 20 newborn babies were studied cytogenetically and one case (7%) from OA and TESE showed a sex reversal karyotype (a male infant with 46,XX). CONCLUSION: Frozen-thawed spermatozoa from various types of azoospermia can be used efficiently in planned ICSI cycles. ICSI fertilization and pregnancy rates of these spermatozoa were comparable to those from ejaculated samples. Elevated chromosomal abnormalities in the sperm from NOA may be associated with low pregnancy rates and a large sample size is needed to confirm this hypothesis. Further investigation is needed to determine whether the rate of sex reversal in newborn babies from ICSI is higher than those from the normal population, that our finding is related to the source of sperm used for ICSI, or that this is simply a sporadic event. Supported by: This study is supported by CIHR and the Hospital for Sick Children Foundation.
OTHER: ART Monday, October 18, 2004 2:00 P.M. O-119 Birth weight of singletons born after modified natural cycle IVF compared with singletons born after IVF with ovarian hyperstimulation. M. Keizer, K. Middelburg, N. Vogel, M. J. Pelinck, A. Simons, A. Hoek. University Hospital Groningen, Groningen, Netherlands. OBJECTIVE: The birth weight of singleton children resulting from IVF with controlled ovarian hyperstimulation (COH-IVF), is lower than the birth weight of singletons resulting from spontaneous conceptions. It is hypothesized that this is caused by either ovarian hyperstimulation, IVF laboratory procedures or patient selection. In the present study, birth weights of singletons born after modified natural cycle IVF, in which no ovarian hyperstimulation is performed, were compared to singletons resulting from COH-IVF. DESIGN: Two cohorts were formed. The first cohort consisted of 61 singletons, born between November 2001 and December 2003, all resulting from modified natural cycle IVF. The second cohort consisted of 583 singletons, born between December 1988 and December 2003, all resulting from COH-IVF. Duration of pregnancy and birth weights were compared between cohorts. MATERIALS AND METHODS: For modified natural cycle IVF, the one (or two) oocyte(s) that naturally reaches dominance was used for IVF. No ovarian hyperstimulation was applied. The GnRH-antagonist cetrorelix was administered to prevent untimely LH-surges. In the majority of cases, one single embryo was available for transfer. For COH-IVF, a downregulation or flare-up protocol was used, aiming at about ten oocytes and transfer of two or three embryos. RESULTS: Results are shown in the table.
Patient age, parity and duration of pregnancy were not different between groups. Birth weights were significantly (P ⫽ 0.003) larger in the modified natural cycle IVF group compared to the COH-IVF group. CONCLUSION: Singletons born after modified natural cycle have significantly larger birth weights compared to singletons resulting from COHIVF. Since the laboratory procedure is equal in both groups, we hypothesize that this difference is caused by lack of ovarian hyperstimulation. However, patient selection can not be excluded. Supported by: This study was supported by a grant from the University Hospital Groningen and from Zon-Mw, the Netherlands.
Monday, October 18, 2004 2:15 P.M. O-120 Early evidence of efficacy and safety for a novel sustained-release recombinant human follicle stimulating hormone (FSH-SR). T. Mathews, L. M. Gibbons, A. Priestley, S. Woods, D. W. Warne, L. O’Dea. Bourn Hall Clinic, Cambridge, United Kingdom; Serono International SA, Geneva, Switzerland; Serono, Inc., Rockland, MA. OBJECTIVE: Recombinant hFSH is widely utilized for induction of ovulation in oligo-anovulatory infertility and for stimulation of multiple follicular development in ART. Over the course of a stimulation cycle and depending on the treatment protocol, a patient may self-inject more than 40 times, and have to repeat the process over a number of cycles. A sustainedrelease (SR) preparation of r-hFSH (follitropin alfa for injection) would offer advantages to the patient, nurse and physician ⫺ fewer injections, improved compliance, and a reduced potential for medication errors. FSH-SR was developed in conjunction with Alkermes, Cambridge, MA, USA using follitropin alfa and Alkermes’ patented ProLease® technology. The present study was performed to assess the suitability of this novel formulation of FSH-SR for ovarian stimulation through the monitoring of safety and pharmacodynamic markers (follicle growth and estradiol [E2] production) following its administration to healthy women volunteers. DESIGN: Prospective, open-label, single-center IRB approved study. MATERIALS AND METHODS: 36 healthy, normally-cycling women with normal baseline reproductive hormone values were enrolled. Subjects were treated in sequential groups of 4 with a single dose of FSH-SR administered SC. Five groups (n⫽20) were down-regulated with a GnRH analogue, goserelin acetate, and 4 groups (n⫽16) were studied in spontaneous cycles. Based on a prospectively defined algorithm, the dose of each group was chosen by a Study Steering Committee. Serum FSH, follicular response as assessed by ultrasound, and serum E2 were assessed at baseline and for 49 days after injection. Safety assessments were performed on each patient visit. The main outcome measure was follicle growth as assessed by the number and size of follicles, and serum E2 over time. RESULTS: Following the dosing algorithm, downregulated subjects were administered single doses of 146 mcg, 73 mcg, 218 mcg (x2) and 328 mcg in groups of 4. Non-downregulated subjects were administered 146 mcg, 218 mcg, 73 mcg and 36 mcg. All dose groups showed evidence of FSH effect with a rise in serum E2 and follicular growth. Higher doses were associated with pre-ovulatory E2 values (⬎3500 pmol/mL), with follicles of 20 mm diameter and up to 24 responding follicles (⬎11 mm). Duration of effect, as assessed by days of rising E2 values, was also dose-dependent and up to 10 days (median 4 –9 days). Down-regulation was associated with slower increases in serum E2 and follicle number. FSH-SR was welltolerated in the doses administered, generally and locally, by the study subjects. There were no serious adverse events. CONCLUSION: A FSH-SR dose-dependent effect is identified on follicular development and E2 production. Pre-ovulatory E2 levels and mature follicle development are achieved with a single dose of FSH-SR. FSH-SR was well tolerated by volunteers and may offer a novel option as initial treatment in both OI and ART. Supported by: Serono
Monday, October 18, 2004 2:30 P.M. O-121 Genomic and proteomic analyses of the endometrium during the window of implantation following laser capture microdissection: Compar-
S48
Abstracts
Vol. 82, Suppl. 2, September 2004