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The incidence of mosaicism is not associated with advanced maternal age or diminished ovarian reserve
References: 1. Leach RE, Moghissi KS, Randolph JF, et al. Intensive hormone monitoring in women with unexplained infertility: evidence for subtle abnormalities suggestive of diminished ovarian reserve. Fertil Steril 1997;68(3):413-20. 2. Randolph JF, Ginsburg KA, Leach RE, et al. Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics. Fertil Steril 2003;80(2):320-7. P-289 Tuesday, October 31, 2017 CHRONOLOGICAL AGE IS BETTER THAN PHYSIOLOGICAL AGE AT PREDICTING LIKELIHOOD OF PRODUCING EUPLOID EMBRYOS. T. G. Nazem,a L. Sekhon,a C. Hernandez-Nieto,a J. A. Lee,a C. Briton-Jones,a A. B. Copperman,b D. E. Stein.c,d aReproductive Medicine Associates of New York, New York, NY; bObstetrics and Gynecology, RMANY-Mount Sinai, New York, NY; cReproductive Endocrinology, Reproductive Medicine Associates of New York, New York, NY; dOBGYN and Reproductive Science, Icahn School of Medicine at Mount Sinai West, New York, NY. OBJECTIVE: Transfer of a single euploid embryo results in high implantation and low miscarriage rates as well as decreases the risk of multiple gestations. In some cycles, not a single euploid embryo is produced. This study aimed to compare the relative importance of factors contributing to the development of at least one euploid embryo. DESIGN: Retrospective MATERIALS AND METHODS: Patients who underwent IVF cycles from 2012-2017 were included. Oocyte donation cycles were excluded. Trophectoderm biopsy and pre-implantation genetic testing (PGT) were performed on all embryos. Patient age, BMI, ovarian reserve testing, peak estradiol (E2) and progesterone (P4), number of oocytes retrieved, number of 2PN, cleavage and blastocyst embryos, and number of embryos biopsied were recorded. Data was analyzed using a student’s t-test and logistic regression. RESULTS: A total of 2452 IVF cycles were performed, of which 1859 resulted in a euploid embryo and 593 resulted in no embryos suitable for transfer. Patients who achieved a euploid embryo were younger (36.1 3.9 vs. 39.8 3.5, p< .01), had a lower FSH (6.3 3.0 vs. 7.1 3.7, p < .01), higher AMH (3.6 4.2 vs. 2.0 3.3, p< .01) and higher antral follicle count (12.8 6.5 vs. 8.6 4.7, p< .01) than those with no euploid embryos. There was a difference in the number of embryos available for biopsy between groups. The chance of obtaining a euploid embryo was increased almost two-fold for every additional embryo that developed to blastocyst stage (95% CI 1.5-2.0). Collectively, for every additional year of age there was an 18% decrease in likelihood of having a euploid embryo (95% CI 0.8-0.9). Given the curvilinear nature of the model, the relative odds of obtaining a euploid embryo diminishes multiplicatively with advancing age. The logistic regression equation below most accurately predicts likelihood of euploidy: ‘‘lnpYi¼EuploidXi1-p(Yi¼EuploidjXi) ¼ 6.96 + -0.2 (oocyte age) + -7.9^10-6 (total gonadotropin dose) + -0.0005 (Peak E2) + 0.04 (Peak P4) +0.005 (FSH) + -0.02 (AMH) + 0.04 (Antral follicle count) + -0.004 (Oocytes Retrieved) + 0.006 (2PN) + -0.02 (Cleavage Stage Embryos) + -0.04 (Blastocyst Count) + 0.5 (Blastocysts Biopsied) + 0.3 (SGD testing)’’ CONCLUSIONS: PGT provides precise genomic information that allows providers to better counsel and care for patients. The study demonstrated that while on average there is an 18% annual decreased odds of creating at least one euploid embryo per cycle, the slope of this relationship changes from horizontal in a woman’s twenties to nearly vertical in her forties. Maternal age is a better predictor of obtaining a euploid embryo than ovarian reserve markers. P-290 Tuesday, October 31, 2017 THE INCIDENCE OF MOSAICISM IS NOT ASSOCIATED WITH ADVANCED MATERNAL AGE OR DIMINISHED OVARIAN RESERVE. L. Sekhon,a J. Feuerstein,b T. G. Nazem,c C. Briton-Jones,d J. A. Lee,d L. Grunfeld,d A. B. Copperman.e aReproductive Medicine Associates New York, New York, NY; bTouro College of Osteopathic Medicine, New City, NY; cRMA of New York, New York, NY; dReproductive Medicine Associates of New York, New York, NY; eObstetrics and Gynecology, RMANY-Mount Sinai, New York, NY.
FERTILITY & STERILITYÒ
OBJECTIVE: Targeted next generation sequencing (NGS) is now utilized for embryonic aneuploidy screening. The increased resolution of NGS presents the opportunity to detect mosacism. While a direct relationship between advanced maternal age and aneuploidy is well established, the data linking ovarian age and mosaicism is limited. Although mosaicism results from mitotic errors, advanced ovarian age could theoretically hinder the proper segregation of chromosomes via defects in cohesion molecules and microtubules. The study evaluated whether there is an association between mosaicism and either advanced maternal age or diminished ovarian reserve. DESIGN: Retrospective, observational study MATERIALS AND METHODS: The study included patients undergoing freeze-all autologous IVF cycles with targeted NGS for preimplantation genetic testing (PGT) from 2016 to 2017. Trophectoderm cells underwent biopsy and aneuploidy screening. Patients were stratified by age as suggested by the Society for Assisted Reproductive Technology (SART). Chi-square test and binary and linear logistic regression analysis were used. RESULTS: A total of 315 patients had 1809 blastocysts screened for aneuploidy with targeted NGS, with a 9.4% (n¼170) rate of mosaicism. There was no significant difference in the rate of mosaicism according to patient age (x2¼8.58, p¼0.072) (Table 1). The odds of mosaicism was not modified by maternal age (OR 0.98 [95% CI 0.9-1.1], p¼0.63), AMH (OR 1.0 [95% CI 0.99-1.02], p¼0.7, basal antral follicle count (BAFC) (OR 1.01 [95% CI 0.91.06], p¼0.6) or BMI (OR 0.96 [95% CI 0.9-1.04], p¼0.3. The likelihood of mosaicism increased with the number of blastocysts biopsied (OR 1.4 [95% CI 1.2-1.6], p<0.0001). Table 1. Mosaicism rate according to SART Age Groups NGS (N¼315)
A: <35 (N¼114)
B: 35-37 (N¼82)
C: 38-40 (N¼83)
D: 41-42 (N¼29)
E: >42 (N¼7)
Embryos Biopsied (N¼1809)
9.7% (79/818)
12.3% (57/460)
6.1% (24/395)
8.7% (10/115)
0.0% (0/21)
P-value 0.0723
CONCLUSIONS: This study showed no correlation between the incidence of embryonic mosaicism and patient age or ovarian reserve. Unlike meiotically derived aneuploidy, mosaicism arises from impaired mitotic chromosome segregation which does not appear to increase with ovarian age. While mosaicism is acknowledged to be a pathological phenomenon arising during preimplantation embryonic development- until recently, predisposing factors and the precise frequency with which it occurs could not be studied. With increased use of NGS for PGT, future studies will allow deeper investigation into clinical, treatment and patient factors that are correlated with the occurrence of mosaicism. P-291 Tuesday, October 31, 2017 CYCLE DAY 2 IGF-1 LEVELS ARE PREDICTIVE OF NEGATIVE PREGNANCY OUTCOME IN POOR RESPONDERS. J. Lekovich,a L. Man,a C. Canon,b N. Pereira,a D. James.a aThe Ronald O. Perelman and Claudia Cohen CRM, Weill Cornell Medicine, New York, NY; bObstetrics and Gynecology, New York Presbyterian Hospital - Weill Cornell Medicine, New York, NY. OBJECTIVE: Follicle stimulating hormone (FSH) requires IGF-1 signaling for follicular growth and maturation. Only a small proportion of antral follicles (or none) develops during controlled ovarian hyperstimulation (COH) in poor responders despite administration high doses of FSH. Chronic relative elevation of IGF-1 leads to receptor resistance and decreased IGF signaling in the ovary. We sought to investigate if serum IGF-1 levels on cycle day 2 (CD2) correlate with response to COH and if they can be predictive of a IVF cycle outcome. DESIGN: Retrospective cohort. MATERIALS AND METHODS: All women between 21-41 years-old with body mass index (BMI) between 18-30kg/m2 who have undergone in vitro fertilization (IVF) without estrogen patch or oral contraceptive pill pre-treatment at our institution between 2013 and 2015 were included. They were separated into 3 groups: poor responders (<5 oocytes retrieved), normal responders (8-12 oocytes retrieved) and high responders (>18 oocytes retrieved). Primary outcome: CD2 IGF1 serum levels, Anti-Mullerian Hormone (AMH), antral follicle count (AFC). ROC curve was used to determine sensitivity/specificity of CD2 IGF1 serum levels in regards to negative pregnancy outcome.
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FERTILITY & STERILITYÒ
OBJECTIVE: Targeted next generation sequencing (NGS) is now utilized for embryonic aneuploidy screening. The increased resolution of NGS presents the opportunity to detect mosacism. While a direct relationship between advanced maternal age and aneuploidy is well established, the data linking ovarian age and mosaicism is limited. Although mosaicism results from mitotic errors, advanced ovarian age could theoretically hinder the proper segregation of chromosomes via defects in cohesion molecules and microtubules. The study evaluated whether there is an association between mosaicism and either advanced maternal age or diminished ovarian reserve. DESIGN: Retrospective, observational study MATERIALS AND METHODS: The study included patients undergoing freeze-all autologous IVF cycles with targeted NGS for preimplantation genetic testing (PGT) from 2016 to 2017. Trophectoderm cells underwent biopsy and aneuploidy screening. Patients were stratified by age as suggested by the Society for Assisted Reproductive Technology (SART). Chi-square test and binary and linear logistic regression analysis were used. RESULTS: A total of 315 patients had 1809 blastocysts screened for aneuploidy with targeted NGS, with a 9.4% (n¼170) rate of mosaicism. There was no significant difference in the rate of mosaicism according to patient age (x2¼8.58, p¼0.072) (Table 1). The odds of mosaicism was not modified by maternal age (OR 0.98 [95% CI 0.9-1.1], p¼0.63), AMH (OR 1.0 [95% CI 0.99-1.02], p¼0.7, basal antral follicle count (BAFC) (OR 1.01 [95% CI 0.91.06], p¼0.6) or BMI (OR 0.96 [95% CI 0.9-1.04], p¼0.3. The likelihood of mosaicism increased with the number of blastocysts biopsied (OR 1.4 [95% CI 1.2-1.6], p<0.0001). Table 1. Mosaicism rate according to SART Age Groups NGS (N¼315)
A: <35 (N¼114)
B: 35-37 (N¼82)
C: 38-40 (N¼83)
D: 41-42 (N¼29)
E: >42 (N¼7)
Embryos Biopsied (N¼1809)
9.7% (79/818)
12.3% (57/460)
6.1% (24/395)
8.7% (10/115)
0.0% (0/21)
P-value 0.0723
CONCLUSIONS: This study showed no correlation between the incidence of embryonic mosaicism and patient age or ovarian reserve. Unlike meiotically derived aneuploidy, mosaicism arises from impaired mitotic chromosome segregation which does not appear to increase with ovarian age. While mosaicism is acknowledged to be a pathological phenomenon arising during preimplantation embryonic development- until recently, predisposing factors and the precise frequency with which it occurs could not be studied. With increased use of NGS for PGT, future studies will allow deeper investigation into clinical, treatment and patient factors that are correlated with the occurrence of mosaicism. P-291 Tuesday, October 31, 2017 CYCLE DAY 2 IGF-1 LEVELS ARE PREDICTIVE OF NEGATIVE PREGNANCY OUTCOME IN POOR RESPONDERS. J. Lekovich,a L. Man,a C. Canon,b N. Pereira,a D. James.a aThe Ronald O. Perelman and Claudia Cohen CRM, Weill Cornell Medicine, New York, NY; bObstetrics and Gynecology, New York Presbyterian Hospital - Weill Cornell Medicine, New York, NY. OBJECTIVE: Follicle stimulating hormone (FSH) requires IGF-1 signaling for follicular growth and maturation. Only a small proportion of antral follicles (or none) develops during controlled ovarian hyperstimulation (COH) in poor responders despite administration high doses of FSH. Chronic relative elevation of IGF-1 leads to receptor resistance and decreased IGF signaling in the ovary. We sought to investigate if serum IGF-1 levels on cycle day 2 (CD2) correlate with response to COH and if they can be predictive of a IVF cycle outcome. DESIGN: Retrospective cohort. MATERIALS AND METHODS: All women between 21-41 years-old with body mass index (BMI) between 18-30kg/m2 who have undergone in vitro fertilization (IVF) without estrogen patch or oral contraceptive pill pre-treatment at our institution between 2013 and 2015 were included. They were separated into 3 groups: poor responders (<5 oocytes retrieved), normal responders (8-12 oocytes retrieved) and high responders (>18 oocytes retrieved). Primary outcome: CD2 IGF1 serum levels, Anti-Mullerian Hormone (AMH), antral follicle count (AFC). ROC curve was used to determine sensitivity/specificity of CD2 IGF1 serum levels in regards to negative pregnancy outcome.
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