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Pregnancy rates after euploid embryo transfer for poor responders in IVF
TABLE 1. Demographic and cycle characteristics of patients grouped according to their serum P4 levels on the day of trigger.
Age (years) BMI (kg/m2) Race White African American Hispanic Asian Hawaiian/Pacific Unknown Maximum historical FSH (IU/L) Antral follicle count Gravida (n,%) Nulligravid Multigravid Parity (n,%) Nulliparous Multiparous Days of stimulation Type of suppression Agonist Antagonist None Total gonadotropin used (IU) Peak estradiol (pg/ml) Total number of mature oocytes Day of transfer 3 5 Other Number of embryos transferred Number of embryos cryopreserved
P4 < 1.1 ng/ml (n¼283)
P4 R 1.1 ng/ml (n¼95)
35.7 0.3 27.3 0.4
36.1 0.5 25.6 0.5
79 (28) 34 (12.1) 43 (15.3) 16 (5.7) 1 (0.3) 109 (38.6) 8.1 0.2
27 (28.7) 10 (10.6) 6 (6.4) 10 (10.6) 1 (1.1) 40 (42.6) 7.5 0.2
13.0 0.5
12.6 0.6
113 (40.1) 169 (59.9)
40 (42.1) 55 (57.9)
185 (65.4) 98 (34.6) 10.5 0.1
70 (73.7) 25 (26.3) 10.9 0.2
191 (67.5) 84 (29.7) 8 (2.8) 3003.2 87.6
60 (63.2) 34 (35.8) 1 (1) 3306.5 172.7
0.1
1447.8 49.6 9.5 0.4
1643.7 77.0 11.7 0.6
0.04 0.0001
178 (62.9) 94 (33.2) 11 (3.9) 2.2 0.1
56 (59) 35 (36.8) 4 (4.2) 2.5 0.1
0.1
0.9 0.1
0.9 0.2
1
p 0.5 0.02 0.1
0.2 0.8 0.7 0.1 0.07 0.5
0.8
test, Mann-Whitney U, chi-square and logistic regression analyses were used. Data was expressed as mean SD or percentage and p<0.05 was considered significant. RESULTS: The clinical pregnancy rates according to serum P4 levels on the day of hCG trigger are presented in Figure 1. There was a significant negative correlation between serum P4 levels and clinical pregnancy rates in fresh cycles, especially for P4 levels >1ng/ml (r¼-0.9, p¼0.04). The demographic and cycle characteristics of patients grouped according to their serum P4 levels (> or %1.1ng/ml) are presented in Table 1. After controlling for BMI, days of stimulation, peak estradiol, and total number of mature oocytes, serum P4 level R1.1ng/ml was associated with lower clinical pregnancy rates when compared to serum P4 levels <1.1ng/ml (OR: 0.57, 95% CI: 0.34-0.95). CONCLUSIONS: Serum P4 levels R1.1ng/ml on day of hCG trigger are associated with lower pregnancy rates in fresh cycles. Freezing all embryos when serum P4 levels are R1.1 followed by frozen embryo transfer may increase clinical pregnancy rates. FINANCIAL SUPPORT: None. References: 1. Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60,000 cycles. Hum Reprod Update 2013;19:433-57.
P-48 PREGNANCY RATES AFTER EUPLOID EMBRYO TRANSFER FOR POOR RESPONDERS IN IVF. L. A. Kaye, M. C. Antero, A. F. Bartolucci, L. Engmann, C. A. Benadiva, J. C. Nulsen. Center for Advanced Reproductive Services, University of Connecticut, Farmington, CT, USA.
e34
PCRS Abstracts
BACKGROUND: Women with a previous or expected poor response to IVF stimulation and transfer often opt to undergo preimplantation genetic screening (PGS) in an attempt to eliminate aneuploidy as a possible cause for implantation failure or miscarriage. However, it is not clear whether PGS in poor responders suitably improves outcomes as it does in a normal or high responding couple. One study found that poor responders were less likely to achieve an embryo transfer after PGS, but those who did had similar rates of pregnancy and miscarriage (1). OBJECTIVE: To compare ongoing pregnancy rates after euploid embryo transfer between poor responders (PORs) and normal or high responders. MATERIALS AND METHODS: Fresh and cryopreserved autologous transfers of euploid blastocysts performed at 23 North American IVF centers between 2013-2015 were identified in this multicenter retrospective cohort study. Women ages 18-49 years undergoing all stimulation protocols were included. Euploidy was determined by biopsy and PGS using Fluorescence In-Situ Hybridization, Comparative Genomic Hybridization or Next Generation Sequencing. Poor responders were defined by Bologna criteria including at least two out of three features: 1) advanced maternal age (R40 years) or any other risk factor for POR; 2) a previous POR (%3 oocytes with a conventional stimulation protocol); or 3) an abnormal ovarian reserve test (ORT), antral follicle count (AFC) <7 or serum anti-Mullerian hormone (AMH) <1.1 ng/mL. Cycle outcomes included clinical pregnancy rates (CPR), ongoing pregnancy rates (OPR), and miscarriage rates. Chi-square test was used for categorical variables. RESULTS: A total of 1799 euploid blastocyst transfers were included. 222 transfers were performed in PORs (12.3%). In PORs the CPR was 56.8% and the OPR was 52.3% compared to 66.3% and 63.7% respectively in the remaining cycles (p¼0.005 and p¼0.001). Clinical miscarriages occurred in 17.5% of pregnant PORs compared to 12.8% in normal/high responders (p¼0.15). Additionally, PORs had a biochemical pregnancy rate of 14.0% versus 9.6% in normal/high responders (p¼0.042). As PGS decreases the effects of aneuploidy, this technique is considered to increase pregnancy rates in women of advanced maternal age. Looking at all responders 40 years or older at the time of oocyte retrieval (n¼335), the CPR was 62.4%, OPR was 60.0%, and clinical miscarriage rate was 15.3%. This compares to a miscarriage rate of 12.9% in women younger than 40 years (p¼0.68). CONCLUSIONS: There are significant differences among pregnancy and biochemical rates when comparing PORs by Bologna criteria to normal and high responders. However, pregnancy rates for patients undergoing a transfer in the POR group remain high and this technique should be considered to aid reproductive outcomes for this group. Our data also suggest a decreased effect of advancing age on pregnancy and miscarriage rates for women over 40 with the use of PGS when a transfer is attained. SUPPORT: New England Fertility Society honorable mention grant, sponsored by eIVF, a service of PracticeHwy.com References: 1. Setti AS, de Almeida Ferreira Braga DP, de Cassia Savio Figueira R, de Castro Azevedo M, Iaconelli Jr. A, Borges Jr. E. Are poor responders patients at higher risk for producing aneuploid embryos in vitro? J Assist Reprod Genet [Internet] 2011;28(5):399–404. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21110079
P-49 FROZEN EMBRYO TRANSFER OUTCOMES IN SUBSEQUENT IMMEDIATE CYCLES FOLLOWING GNRH AGONIST OR HCG TRIGGERS. L. A. Kaye,a A. Marsidi,a P. Rai,b J. C. Nulsen,a L. Engmann,a C. A. Benadiva.a aDepartment of Obstetrics & Gynecology, University of Connecticut, Farmington, CT, USA; bSchool of Medicine, University of Connecticut, Farmington, CT, USA. BACKGROUND: In IVF, two oocyte maturation trigger modalities are available: the more commonly used human chorionic gonadotropin (hCG) and gonadotropin releasing hormone agonists (GnRHa). GnRHa stimulates an endogenous release of gonadotropins similar to a natural surge, but the shorter duration of the surge and the pituitary down-regulation properties of the drug result in a dysfunctional and shortened luteal phase (1). Prior studies have evaluated the duration of time between stimulation and frozen-thawed embryo transfer (FET) but only one specifically after GnRHa trigger which showed equivalent pregnancy rates (2). The cycle after a GnRHa trigger may have important differences compared to hCG triggered cycles that could impact the success of subsequent FET and warrant investigation.
Vol. 107, No. 3, Supplement, March 2017
Age (years) BMI (kg/m2) Race White African American Hispanic Asian Hawaiian/Pacific Unknown Maximum historical FSH (IU/L) Antral follicle count Gravida (n,%) Nulligravid Multigravid Parity (n,%) Nulliparous Multiparous Days of stimulation Type of suppression Agonist Antagonist None Total gonadotropin used (IU) Peak estradiol (pg/ml) Total number of mature oocytes Day of transfer 3 5 Other Number of embryos transferred Number of embryos cryopreserved
P4 < 1.1 ng/ml (n¼283)
P4 R 1.1 ng/ml (n¼95)
35.7 0.3 27.3 0.4
36.1 0.5 25.6 0.5
79 (28) 34 (12.1) 43 (15.3) 16 (5.7) 1 (0.3) 109 (38.6) 8.1 0.2
27 (28.7) 10 (10.6) 6 (6.4) 10 (10.6) 1 (1.1) 40 (42.6) 7.5 0.2
13.0 0.5
12.6 0.6
113 (40.1) 169 (59.9)
40 (42.1) 55 (57.9)
185 (65.4) 98 (34.6) 10.5 0.1
70 (73.7) 25 (26.3) 10.9 0.2
191 (67.5) 84 (29.7) 8 (2.8) 3003.2 87.6
60 (63.2) 34 (35.8) 1 (1) 3306.5 172.7
0.1
1447.8 49.6 9.5 0.4
1643.7 77.0 11.7 0.6
0.04 0.0001
178 (62.9) 94 (33.2) 11 (3.9) 2.2 0.1
56 (59) 35 (36.8) 4 (4.2) 2.5 0.1
0.1
0.9 0.1
0.9 0.2
1
p 0.5 0.02 0.1
0.2 0.8 0.7 0.1 0.07 0.5
0.8
test, Mann-Whitney U, chi-square and logistic regression analyses were used. Data was expressed as mean SD or percentage and p<0.05 was considered significant. RESULTS: The clinical pregnancy rates according to serum P4 levels on the day of hCG trigger are presented in Figure 1. There was a significant negative correlation between serum P4 levels and clinical pregnancy rates in fresh cycles, especially for P4 levels >1ng/ml (r¼-0.9, p¼0.04). The demographic and cycle characteristics of patients grouped according to their serum P4 levels (> or %1.1ng/ml) are presented in Table 1. After controlling for BMI, days of stimulation, peak estradiol, and total number of mature oocytes, serum P4 level R1.1ng/ml was associated with lower clinical pregnancy rates when compared to serum P4 levels <1.1ng/ml (OR: 0.57, 95% CI: 0.34-0.95). CONCLUSIONS: Serum P4 levels R1.1ng/ml on day of hCG trigger are associated with lower pregnancy rates in fresh cycles. Freezing all embryos when serum P4 levels are R1.1 followed by frozen embryo transfer may increase clinical pregnancy rates. FINANCIAL SUPPORT: None. References: 1. Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60,000 cycles. Hum Reprod Update 2013;19:433-57.
P-48 PREGNANCY RATES AFTER EUPLOID EMBRYO TRANSFER FOR POOR RESPONDERS IN IVF. L. A. Kaye, M. C. Antero, A. F. Bartolucci, L. Engmann, C. A. Benadiva, J. C. Nulsen. Center for Advanced Reproductive Services, University of Connecticut, Farmington, CT, USA.
e34
PCRS Abstracts
BACKGROUND: Women with a previous or expected poor response to IVF stimulation and transfer often opt to undergo preimplantation genetic screening (PGS) in an attempt to eliminate aneuploidy as a possible cause for implantation failure or miscarriage. However, it is not clear whether PGS in poor responders suitably improves outcomes as it does in a normal or high responding couple. One study found that poor responders were less likely to achieve an embryo transfer after PGS, but those who did had similar rates of pregnancy and miscarriage (1). OBJECTIVE: To compare ongoing pregnancy rates after euploid embryo transfer between poor responders (PORs) and normal or high responders. MATERIALS AND METHODS: Fresh and cryopreserved autologous transfers of euploid blastocysts performed at 23 North American IVF centers between 2013-2015 were identified in this multicenter retrospective cohort study. Women ages 18-49 years undergoing all stimulation protocols were included. Euploidy was determined by biopsy and PGS using Fluorescence In-Situ Hybridization, Comparative Genomic Hybridization or Next Generation Sequencing. Poor responders were defined by Bologna criteria including at least two out of three features: 1) advanced maternal age (R40 years) or any other risk factor for POR; 2) a previous POR (%3 oocytes with a conventional stimulation protocol); or 3) an abnormal ovarian reserve test (ORT), antral follicle count (AFC) <7 or serum anti-Mullerian hormone (AMH) <1.1 ng/mL. Cycle outcomes included clinical pregnancy rates (CPR), ongoing pregnancy rates (OPR), and miscarriage rates. Chi-square test was used for categorical variables. RESULTS: A total of 1799 euploid blastocyst transfers were included. 222 transfers were performed in PORs (12.3%). In PORs the CPR was 56.8% and the OPR was 52.3% compared to 66.3% and 63.7% respectively in the remaining cycles (p¼0.005 and p¼0.001). Clinical miscarriages occurred in 17.5% of pregnant PORs compared to 12.8% in normal/high responders (p¼0.15). Additionally, PORs had a biochemical pregnancy rate of 14.0% versus 9.6% in normal/high responders (p¼0.042). As PGS decreases the effects of aneuploidy, this technique is considered to increase pregnancy rates in women of advanced maternal age. Looking at all responders 40 years or older at the time of oocyte retrieval (n¼335), the CPR was 62.4%, OPR was 60.0%, and clinical miscarriage rate was 15.3%. This compares to a miscarriage rate of 12.9% in women younger than 40 years (p¼0.68). CONCLUSIONS: There are significant differences among pregnancy and biochemical rates when comparing PORs by Bologna criteria to normal and high responders. However, pregnancy rates for patients undergoing a transfer in the POR group remain high and this technique should be considered to aid reproductive outcomes for this group. Our data also suggest a decreased effect of advancing age on pregnancy and miscarriage rates for women over 40 with the use of PGS when a transfer is attained. SUPPORT: New England Fertility Society honorable mention grant, sponsored by eIVF, a service of PracticeHwy.com References: 1. Setti AS, de Almeida Ferreira Braga DP, de Cassia Savio Figueira R, de Castro Azevedo M, Iaconelli Jr. A, Borges Jr. E. Are poor responders patients at higher risk for producing aneuploid embryos in vitro? J Assist Reprod Genet [Internet] 2011;28(5):399–404. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21110079
P-49 FROZEN EMBRYO TRANSFER OUTCOMES IN SUBSEQUENT IMMEDIATE CYCLES FOLLOWING GNRH AGONIST OR HCG TRIGGERS. L. A. Kaye,a A. Marsidi,a P. Rai,b J. C. Nulsen,a L. Engmann,a C. A. Benadiva.a aDepartment of Obstetrics & Gynecology, University of Connecticut, Farmington, CT, USA; bSchool of Medicine, University of Connecticut, Farmington, CT, USA. BACKGROUND: In IVF, two oocyte maturation trigger modalities are available: the more commonly used human chorionic gonadotropin (hCG) and gonadotropin releasing hormone agonists (GnRHa). GnRHa stimulates an endogenous release of gonadotropins similar to a natural surge, but the shorter duration of the surge and the pituitary down-regulation properties of the drug result in a dysfunctional and shortened luteal phase (1). Prior studies have evaluated the duration of time between stimulation and frozen-thawed embryo transfer (FET) but only one specifically after GnRHa trigger which showed equivalent pregnancy rates (2). The cycle after a GnRHa trigger may have important differences compared to hCG triggered cycles that could impact the success of subsequent FET and warrant investigation.
Vol. 107, No. 3, Supplement, March 2017