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MIS does not predict clinical pregnancy rates after IVF in all age groups
DESIGN: Mouse, bovine and human ovarian tissues were vitrified by Cryotissue and assessed the post thaw survival of the tissue, and success rates after autotransplantation. MATERIALS AND METHODS: Whole, half and 0.2 mm cubes of BDF1 mouse ovary were vitrified by the Cryotop method (Kuwayama 2005). Tissues were equilibrated in m-199 containing 7.5% EG and 7.5% DMSO and vitrified with m-199 containing 15% EG, 15% DMSO and 0.5 M sucrose by Cryotissue (Kitazato BioPharma, Japan). After thawing by plunging in 1M sucros, cryoprotectants were diluted out using m-199 containing 0.5 sucrose. Growing oocytes in preantral follicles of vitrified-thawed tissue were stained by Hoechst and PI to assess their survival. Bovine tissues were vitrified by Cryotissue as an animal model for human clinical because of the similar size and structure. RESULTS: One hundred percent post-thaw survival was obtained for the oocytes of ovarian tissue. Vitrified ovarian tissue was successfully transplanted into the kidney of SCID mouse with normal growth of follicles. Full grown oocytes were obtained from the allotransplant and then matured, fertilized and cultured in-vitro, resulting in normal young after embryo transfer to the recipient. Eighty–eight percent survival was obtained for bovine ovarian tissue after vitrification. In total 8 ovarian tissues were successfully autotransplanted to 4 cattle. Human ovarian tissue from a cancer patient, and from donors for ovarian transplantation (with informed consent) was vitrified according to the cattle method. After thawing, high post-thaw survival (89%) was obtained. CONCLUSIONS: These results indicate that the ultra rapid cooling vitrification method in the present study has a potential for clinical use in human ovarian tissue cryopreservation. Supported by: None. Figure 1. Relationship between MIS and Clinical Pregnancy Rate Stratified by Age Group.
P-512 MIS DOES NOT PREDICT CLINICAL PREGNANCY RATES AFTER IVF IN ALL AGE GROUPS. N. C. Douglas, J. G. Wang, G. S. Nakhuda, M. M. Shah, R. A. Lobo, M. V. Sauer. Obstetrics and Gynecology, Columbia University, New York, NY. OBJECTIVE: Mu¨llerian inhibiting substance (MIS) has not demonstrated consistent correlation with IVF clinical pregnancy rates (CPR). The objective of this study is to analyze whether this association is affected by patient age. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Serum estradiol, FSH, and MIS were obtained from 524 women (age 37 4) undergoing controlled ovarian hyperstimulation (COH) for IVF. Gonadotropin stimulation, monitoring of ovarian response, hCG injections, oocyte retrievals and embryo transfers were carried out according to established protocols. Patients’ ages were stratified into quartiles (%33, 34–37, 38–41, and R42) and MIS levels into tertiles (%0.5, 1.5–1.49, and R1.50 ng/mL). CPR was defined according to SART. RESULTS: Higher serum MIS is associated with a more mature oocytes (MIIs) retrieved (Table 1). This association is signficant across all age groups, but the mean number of MIIs retrieved in each MIS tertile is the same regardless of age. In women %33, CPR did not vary with MIS (Figure 1). In the 35–38 group, CPRs from the lowest to the highest MIS tertile increased from 0.25 to 0.55 (P<0.01 for the linear association). While the linear trend is also signficant for the 38–41group (P<0.01), higher MIS is not associated with a greater CPR in the 42þ age group. TABLE. Association between MIS (ng/mL) and MIIs retrieved, stratified by age group
Age % 34 Age 35–38 Age 39–41 Age R 42 y
(A) MIS %.5
(B) MIS .5–1.49
(C) MIS R1.5
6.0 0.8 5.0 0.4 5.0 0.3 5.2 0.7
10.1 0.8 y 9.1 0.8 y 7.5 0.6 y 8.2 0.5 y
13.3 0.8* 15.2 1.4* 13.7 1.7* 15.8 2.4*
(A) < (B), P<0.05;* (A) < (C) and (B) < (C), P<0.05.
CONCLUSIONS: The correlation between MIS and MIIs retrieved is strong and not affected by age. MIS correlates well with CPR only for women in the intermediate age range; however, the association is poor on either extremes of the reproductive age. In young patients, high egg quality can
S276
Abstracts
effectively compensate for a low number of MIIs, resulting in similar CPRs across all MIS levels. Conversely, high number of MIIs, associated with greater MIS levels, cannot sufficiently compensate for the low quality oocytes obtained from older patients. Supported by: None.
P-513 RE-DEFINING POOR RESPONDERS ACCORDING TO THEIR CLINICAL OUTCOME. J. Mu~noz, L. Herrero, A. P. de Souza Aguiar, I. Caba~nes, M. Aragones, J. A. Garcıa-Velasco. IVF Laboratory, IVI-Madrid, Madrid, Spain; Integral Women’s Health, Rey Juan Carlos University, Mostoles, Madrid, Spain. OBJECTIVE: Definition of poor response to controlled ovarian hyperstimulation (COH) is still quite empirical and controversial. In order to clarify this issue, we evaluated if the number of retrieved oocytes in IVF/ICSI cycles correlates with clinical outcome; according to this model, we aimed to establish a clinically useful cut-off, below which patients could be classified as low responders. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Between 2005 and 2006, all non-donor IVF/ICSI cycles attending our unit (3626) were included; 1889 were ICSI cycles, 1235 IVF cycles, and 502 cycles a combination of both techniques. Mean age was 35.3 years old. COH was carried out with GnRH analogues and gonadotropins, and final oocyte maturation was achieved with sc administration of hCG (250 mg). IVF/ICSI was carried out according to standard procedures. Clinical pregnancy rate (CPR) was diagnosed by observing a fetal heart beat on ultrasonography at 6 weeks pregnancy. Simple linear regression (SLR) was used to investigate the relationship between the number of oocytes and CPR. RESULTS: A total of 1752 pregnancies were diagnosed in the 3626 IVF/ ICSI cycles performed, resulting in a CPR of 48.3%. No differences were observed between IVF, ICSI, or IVF/ICSI patients. SLR analysis revealed that there was a strong correlation between the number of oocytes retrieved and the CPR obtained (r ¼ 0.83; r2 ¼ 0.69). With further analysis, we found that the best equation to explain this correlation was a double reciprocal equation (%CPR ¼ 1/(1.8253 þ 4.140/n oocytes) (r ¼ 0.97; r2 ¼ 0.95), with describes the curve shown in fig 1. CPR increases with the number of oocytes retrieved, but after 5 oocytes or more the curve reached a plateau, giving similar results with higher number of oocytes. When stratified by
Vol. 88, Suppl 1, September 2007
P-512 MIS DOES NOT PREDICT CLINICAL PREGNANCY RATES AFTER IVF IN ALL AGE GROUPS. N. C. Douglas, J. G. Wang, G. S. Nakhuda, M. M. Shah, R. A. Lobo, M. V. Sauer. Obstetrics and Gynecology, Columbia University, New York, NY. OBJECTIVE: Mu¨llerian inhibiting substance (MIS) has not demonstrated consistent correlation with IVF clinical pregnancy rates (CPR). The objective of this study is to analyze whether this association is affected by patient age. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Serum estradiol, FSH, and MIS were obtained from 524 women (age 37 4) undergoing controlled ovarian hyperstimulation (COH) for IVF. Gonadotropin stimulation, monitoring of ovarian response, hCG injections, oocyte retrievals and embryo transfers were carried out according to established protocols. Patients’ ages were stratified into quartiles (%33, 34–37, 38–41, and R42) and MIS levels into tertiles (%0.5, 1.5–1.49, and R1.50 ng/mL). CPR was defined according to SART. RESULTS: Higher serum MIS is associated with a more mature oocytes (MIIs) retrieved (Table 1). This association is signficant across all age groups, but the mean number of MIIs retrieved in each MIS tertile is the same regardless of age. In women %33, CPR did not vary with MIS (Figure 1). In the 35–38 group, CPRs from the lowest to the highest MIS tertile increased from 0.25 to 0.55 (P<0.01 for the linear association). While the linear trend is also signficant for the 38–41group (P<0.01), higher MIS is not associated with a greater CPR in the 42þ age group. TABLE. Association between MIS (ng/mL) and MIIs retrieved, stratified by age group
Age % 34 Age 35–38 Age 39–41 Age R 42 y
(A) MIS %.5
(B) MIS .5–1.49
(C) MIS R1.5
6.0 0.8 5.0 0.4 5.0 0.3 5.2 0.7
10.1 0.8 y 9.1 0.8 y 7.5 0.6 y 8.2 0.5 y
13.3 0.8* 15.2 1.4* 13.7 1.7* 15.8 2.4*
(A) < (B), P<0.05;* (A) < (C) and (B) < (C), P<0.05.
CONCLUSIONS: The correlation between MIS and MIIs retrieved is strong and not affected by age. MIS correlates well with CPR only for women in the intermediate age range; however, the association is poor on either extremes of the reproductive age. In young patients, high egg quality can
S276
Abstracts
effectively compensate for a low number of MIIs, resulting in similar CPRs across all MIS levels. Conversely, high number of MIIs, associated with greater MIS levels, cannot sufficiently compensate for the low quality oocytes obtained from older patients. Supported by: None.
P-513 RE-DEFINING POOR RESPONDERS ACCORDING TO THEIR CLINICAL OUTCOME. J. Mu~noz, L. Herrero, A. P. de Souza Aguiar, I. Caba~nes, M. Aragones, J. A. Garcıa-Velasco. IVF Laboratory, IVI-Madrid, Madrid, Spain; Integral Women’s Health, Rey Juan Carlos University, Mostoles, Madrid, Spain. OBJECTIVE: Definition of poor response to controlled ovarian hyperstimulation (COH) is still quite empirical and controversial. In order to clarify this issue, we evaluated if the number of retrieved oocytes in IVF/ICSI cycles correlates with clinical outcome; according to this model, we aimed to establish a clinically useful cut-off, below which patients could be classified as low responders. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Between 2005 and 2006, all non-donor IVF/ICSI cycles attending our unit (3626) were included; 1889 were ICSI cycles, 1235 IVF cycles, and 502 cycles a combination of both techniques. Mean age was 35.3 years old. COH was carried out with GnRH analogues and gonadotropins, and final oocyte maturation was achieved with sc administration of hCG (250 mg). IVF/ICSI was carried out according to standard procedures. Clinical pregnancy rate (CPR) was diagnosed by observing a fetal heart beat on ultrasonography at 6 weeks pregnancy. Simple linear regression (SLR) was used to investigate the relationship between the number of oocytes and CPR. RESULTS: A total of 1752 pregnancies were diagnosed in the 3626 IVF/ ICSI cycles performed, resulting in a CPR of 48.3%. No differences were observed between IVF, ICSI, or IVF/ICSI patients. SLR analysis revealed that there was a strong correlation between the number of oocytes retrieved and the CPR obtained (r ¼ 0.83; r2 ¼ 0.69). With further analysis, we found that the best equation to explain this correlation was a double reciprocal equation (%CPR ¼ 1/(1.8253 þ 4.140/n oocytes) (r ¼ 0.97; r2 ¼ 0.95), with describes the curve shown in fig 1. CPR increases with the number of oocytes retrieved, but after 5 oocytes or more the curve reached a plateau, giving similar results with higher number of oocytes. When stratified by
Vol. 88, Suppl 1, September 2007