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Blastocyst transfers improve pregnancy rates for select older patients, but not for those under 37 years old
CONCLUSION: By comparing these observations, we conclude that our transferring technique has reached an efficiency of 94% or greater (as some of the failures may be attributable to lack of uterine receptivity or to immune factors). Supported by: None
P-191 Assessment of ovarian reserve using follicle stimulating hormone (FSH) isoforms to predict outcome with in vitro fertilization (IVF). G. S. Letterie, V. Padmanabhan. Center for Fertility and Reproductive Endocrinology, Virginia Mason Medical Center, Seattle, WA; University of Michigan Reproductive Sciences Program, Ann Arbor, MI. OBJECTIVE: FSH has a critical role in folliculogenesis and is secreted in a variety of molecular forms. The glycosylation variants are influenced by hormonal milieu and are age and cycle sensitive. We hypothesized that FSH isoforms could reliably assess ovarian reserve and identify patients with a low likelihood of success with IVF prior to any observed elevations in serum concentrations of FSH or estradiol on cycle day 3. To study this hypothesis, we compared FSH isoform profiles and content in successful and failed IVF cycles after normal ovarian reserve testing. DESIGN: Prospective, blinded, comparative. MATERIALS AND METHODS: FSH heterogeneity was studied in eight patients divided into two groups. Group I (N⫽4) were poor responders to stimulation during an IVF cycle with the transfer of 2 to 3 poor quality, fragmented embryos not exceeding a 5 to 6 cell stage and no pregnancy. Group II (N⫽4) consisted of oocyte donors who had at least two eight cell embryos available for transfer to a recipient resulting in a clinical, ongoing pregnancy. All patients had day 3 FSH and estradiol concentrations less than 8mIU/mL and 80pg/mL respectively. Chromatofocusing separation was used to determine the isoform distribution pattern of FSH. Immunoreactive FSH content of each fraction was analyzed in segments corresponding to 0.5 pH units from pH 7.0 to 4.0 and for the degree of acidity (less and greater than pH 4.6) for each group. RESULTS: The ages of the patients in Groups I and II were 34 (⫽/-1.0) and 27 (⫾1.2) respectively [age in years ⫾SE]. A distinct pattern was noted in the FSH isoforms as follows. Significant differences between Groups I and II were noted in the percent FSH eluted in the pH range of 4.51 to 5.0 (12.6⫾1.4 vs 18.1 ⫾1.5 [mean⫾SE] respectively. No differences in percent FSH eluted was noted in the pH ranges of 5.51 to 6.0 (1.6⫾0.6 vs 1.7⫾0.9) 5.0 to 5.5 (7.1 ⫾ 0.4 vs 5.7 ⫾ 1.1), 4.41 to 4.5 (16.7⫾3.4 vs 16.1⫾0.8) and less than 4.0 (9.4 ⫾3.3 vs 9.14 ⫾2.4). No differences were noted in FSH elution in the salt peak (51.2⫾ 4.0 vs 49.7 ⫾6.1). All data expressed as mean ⫾ standard error for Groups I and II respectively. CONCLUSION: These data suggest a distinct profile and differential secretion of FSH isoforms in patients with normal versus diminished ovarian reserve and reproductive potential. These changes occur before any detectable elevation in day 3 FSH concentrations and may provide a more sensitive assessment of ovarian reserve in patients with normal screening tests. The physiologic significance of this pleomorphism in these two clinical circumstances may be related to changes in follicular dynamics associated with diminished oocyte quality. Alterations in FSH isoforms may provide insight into early changes in pituitary-ovarian dynamics associated with reproductive aging and offer unique opportunities to assess ovarian reserve. Supported by: Supported by unrestricted educational grant from Organon.
P-192 Blastocyst transfers improve pregnancy rates for select older patients, but not for those under 37 years old. J. Mellon, M. R. Fluker, A. A. Yuzpe, D. A. Kelk. Genesis Fertility Center, Vancouver, BC, Canada; University of Colorado Health Sciences Center, Aurora, CO. OBJECTIVE: To compare the results of day 3 versus blastocyst transfers related to maternal age DESIGN: A retrospective analysis of all fresh embryo transfers (n⫽569) performed in 2003. MATERIALS AND METHODS: Blastocyst culture was attempted routinely in women ⱖ 37 yrs, and selectively in younger women requesting an elective single embryo transfer or with repeated unsuccessful cycles. Cul-
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ture to blastocyst stage required at least one surplus good quality 6 – 8 cell embryo beyond the age-specific number needed for day 3 transfer (that is, ⬍ 37 yrs, 2 embryos; 37–39 yrs, 3 embryos; ⬎ 39 yrs, 4 embryos). RESULTS: In 105/569 (18.5%) cycles, the criteria for attempting blast cyst culture were met and at least one blastocyst was obtained in each case. Elective single blastocyst transfer was performed in 28/105 (27%), while 77/105 (73%) had 2 blastocysts transferred. Results are summarized in Table 1. Table 1: Outcome results of day 3 and blastocyst transfers.
Patients ⬍ 37 yrs had similar implantation rates with day 3 or blastocyst transfer. Pregnancy rates were lower in the younger patients receiving blastocysts, largely due to the number of elective single embryo transfers, and perhaps also because a number of “poor prognosis” younger patients were selected to have blastocyst transfer. In women ⱖ 37 yrs, implantation rates were significantly higher in the blastocyst group, resulting in higher pregnancy rates despite the transfer of fewer embryos. The overall twin rate for all ages was not significantly different between day 3(31%) and blastocyst (32%), when ⱖ 2 embryos were transferred. CONCLUSION: In this selected population of patients with supernumerary good quality embryos on day 3, further culture to the blastocyst stage did not improve implantation rates for younger women (⬍ 37 yrs). This is potentially related to lower rates of aneuploidy in younger women, allowing good embryos to be selected just as easily on day 3. However, in women ⱖ 37 yrs with supernumerary good quality embryos on day 3, blastocyst transfer provided a distinct advantage, yielding better implantation and pregnancy rates with the transfer of fewer embryos, thus reducing the potential for higher- order multiple pregnancies. (The authors gratefully acknowledge the important contribution of Z.Liu and N. Maia to the developement of the blastocyst culture system). Supported by: None.
P-193 Elective single blastocyst transfer: Cumulative outcomes from the fresh and subsequent frozen cycles. A. A. Milki, M. D. Hinckley, R. B. Lathi, L. M. Westphal, B. Behr. Stanford University School of Medicine, Stanford, CA. OBJECTIVE: A singleton healthy pregnancy is the ideal outcome of an IVF cycle. As blastocyst transfer has been shown to have an increased implantation rate over cleavage stage transfer in several reports, single embryo transfer (SET) should ideally be performed at the blastocyst stage assuming good results can be obtained with both the fresh and subsequent frozen transfer cycles. The purpose of this study is to report our experience with elective single blastocyst transfer in fresh cycles as well as the cumulative success achieved with the ensuing thaw blastocyst transfers. DESIGN: Retrospective case series MATERIALS AND METHODS: 30 patients elected to have a single blastocyst transfer (SBT) performed with cryopreservation of the remaining blastocysts in order to avoid a multiple gestation pregnancy. All patients used their own oocytes. Sequential culture with P1/Blastocyst Media (Irvine Scientific) or Quinn’s Advantage Cleavage/Blastocyst Media (Sage Biopharma) was used. The blastocyst with the best defined inner cell mass and trophectoderm and the greatest degree of expansion was chosen for transfer. Patient characteristics including age, number of oocytes, zygotes, embryos cryopreserved, and reason for single embryo transfer were recorded. RESULTS: SBT was performed in 6 patients because of anatomic uterine anomalies (2 incompetent cervix, 2 bicornuate uteri, 1 unicornuate uterus, 1 DES exposure,) while the remaining 24 patients opted to avoid twins due to
Vol. 82, Suppl. 2, September 2004
P-191 Assessment of ovarian reserve using follicle stimulating hormone (FSH) isoforms to predict outcome with in vitro fertilization (IVF). G. S. Letterie, V. Padmanabhan. Center for Fertility and Reproductive Endocrinology, Virginia Mason Medical Center, Seattle, WA; University of Michigan Reproductive Sciences Program, Ann Arbor, MI. OBJECTIVE: FSH has a critical role in folliculogenesis and is secreted in a variety of molecular forms. The glycosylation variants are influenced by hormonal milieu and are age and cycle sensitive. We hypothesized that FSH isoforms could reliably assess ovarian reserve and identify patients with a low likelihood of success with IVF prior to any observed elevations in serum concentrations of FSH or estradiol on cycle day 3. To study this hypothesis, we compared FSH isoform profiles and content in successful and failed IVF cycles after normal ovarian reserve testing. DESIGN: Prospective, blinded, comparative. MATERIALS AND METHODS: FSH heterogeneity was studied in eight patients divided into two groups. Group I (N⫽4) were poor responders to stimulation during an IVF cycle with the transfer of 2 to 3 poor quality, fragmented embryos not exceeding a 5 to 6 cell stage and no pregnancy. Group II (N⫽4) consisted of oocyte donors who had at least two eight cell embryos available for transfer to a recipient resulting in a clinical, ongoing pregnancy. All patients had day 3 FSH and estradiol concentrations less than 8mIU/mL and 80pg/mL respectively. Chromatofocusing separation was used to determine the isoform distribution pattern of FSH. Immunoreactive FSH content of each fraction was analyzed in segments corresponding to 0.5 pH units from pH 7.0 to 4.0 and for the degree of acidity (less and greater than pH 4.6) for each group. RESULTS: The ages of the patients in Groups I and II were 34 (⫽/-1.0) and 27 (⫾1.2) respectively [age in years ⫾SE]. A distinct pattern was noted in the FSH isoforms as follows. Significant differences between Groups I and II were noted in the percent FSH eluted in the pH range of 4.51 to 5.0 (12.6⫾1.4 vs 18.1 ⫾1.5 [mean⫾SE] respectively. No differences in percent FSH eluted was noted in the pH ranges of 5.51 to 6.0 (1.6⫾0.6 vs 1.7⫾0.9) 5.0 to 5.5 (7.1 ⫾ 0.4 vs 5.7 ⫾ 1.1), 4.41 to 4.5 (16.7⫾3.4 vs 16.1⫾0.8) and less than 4.0 (9.4 ⫾3.3 vs 9.14 ⫾2.4). No differences were noted in FSH elution in the salt peak (51.2⫾ 4.0 vs 49.7 ⫾6.1). All data expressed as mean ⫾ standard error for Groups I and II respectively. CONCLUSION: These data suggest a distinct profile and differential secretion of FSH isoforms in patients with normal versus diminished ovarian reserve and reproductive potential. These changes occur before any detectable elevation in day 3 FSH concentrations and may provide a more sensitive assessment of ovarian reserve in patients with normal screening tests. The physiologic significance of this pleomorphism in these two clinical circumstances may be related to changes in follicular dynamics associated with diminished oocyte quality. Alterations in FSH isoforms may provide insight into early changes in pituitary-ovarian dynamics associated with reproductive aging and offer unique opportunities to assess ovarian reserve. Supported by: Supported by unrestricted educational grant from Organon.
P-192 Blastocyst transfers improve pregnancy rates for select older patients, but not for those under 37 years old. J. Mellon, M. R. Fluker, A. A. Yuzpe, D. A. Kelk. Genesis Fertility Center, Vancouver, BC, Canada; University of Colorado Health Sciences Center, Aurora, CO. OBJECTIVE: To compare the results of day 3 versus blastocyst transfers related to maternal age DESIGN: A retrospective analysis of all fresh embryo transfers (n⫽569) performed in 2003. MATERIALS AND METHODS: Blastocyst culture was attempted routinely in women ⱖ 37 yrs, and selectively in younger women requesting an elective single embryo transfer or with repeated unsuccessful cycles. Cul-
S202
ture to blastocyst stage required at least one surplus good quality 6 – 8 cell embryo beyond the age-specific number needed for day 3 transfer (that is, ⬍ 37 yrs, 2 embryos; 37–39 yrs, 3 embryos; ⬎ 39 yrs, 4 embryos). RESULTS: In 105/569 (18.5%) cycles, the criteria for attempting blast cyst culture were met and at least one blastocyst was obtained in each case. Elective single blastocyst transfer was performed in 28/105 (27%), while 77/105 (73%) had 2 blastocysts transferred. Results are summarized in Table 1. Table 1: Outcome results of day 3 and blastocyst transfers.
Patients ⬍ 37 yrs had similar implantation rates with day 3 or blastocyst transfer. Pregnancy rates were lower in the younger patients receiving blastocysts, largely due to the number of elective single embryo transfers, and perhaps also because a number of “poor prognosis” younger patients were selected to have blastocyst transfer. In women ⱖ 37 yrs, implantation rates were significantly higher in the blastocyst group, resulting in higher pregnancy rates despite the transfer of fewer embryos. The overall twin rate for all ages was not significantly different between day 3(31%) and blastocyst (32%), when ⱖ 2 embryos were transferred. CONCLUSION: In this selected population of patients with supernumerary good quality embryos on day 3, further culture to the blastocyst stage did not improve implantation rates for younger women (⬍ 37 yrs). This is potentially related to lower rates of aneuploidy in younger women, allowing good embryos to be selected just as easily on day 3. However, in women ⱖ 37 yrs with supernumerary good quality embryos on day 3, blastocyst transfer provided a distinct advantage, yielding better implantation and pregnancy rates with the transfer of fewer embryos, thus reducing the potential for higher- order multiple pregnancies. (The authors gratefully acknowledge the important contribution of Z.Liu and N. Maia to the developement of the blastocyst culture system). Supported by: None.
P-193 Elective single blastocyst transfer: Cumulative outcomes from the fresh and subsequent frozen cycles. A. A. Milki, M. D. Hinckley, R. B. Lathi, L. M. Westphal, B. Behr. Stanford University School of Medicine, Stanford, CA. OBJECTIVE: A singleton healthy pregnancy is the ideal outcome of an IVF cycle. As blastocyst transfer has been shown to have an increased implantation rate over cleavage stage transfer in several reports, single embryo transfer (SET) should ideally be performed at the blastocyst stage assuming good results can be obtained with both the fresh and subsequent frozen transfer cycles. The purpose of this study is to report our experience with elective single blastocyst transfer in fresh cycles as well as the cumulative success achieved with the ensuing thaw blastocyst transfers. DESIGN: Retrospective case series MATERIALS AND METHODS: 30 patients elected to have a single blastocyst transfer (SBT) performed with cryopreservation of the remaining blastocysts in order to avoid a multiple gestation pregnancy. All patients used their own oocytes. Sequential culture with P1/Blastocyst Media (Irvine Scientific) or Quinn’s Advantage Cleavage/Blastocyst Media (Sage Biopharma) was used. The blastocyst with the best defined inner cell mass and trophectoderm and the greatest degree of expansion was chosen for transfer. Patient characteristics including age, number of oocytes, zygotes, embryos cryopreserved, and reason for single embryo transfer were recorded. RESULTS: SBT was performed in 6 patients because of anatomic uterine anomalies (2 incompetent cervix, 2 bicornuate uteri, 1 unicornuate uterus, 1 DES exposure,) while the remaining 24 patients opted to avoid twins due to
Vol. 82, Suppl. 2, September 2004