Pilot clinical study to predict IVF outcomes using embryo mechanical parameters

10-15 mm (Odds ratio (OR) 1.15, 95% Confidence Interval (CI): 1.05-1.25), on CD5 or 6 (OR 1.27, 95% CI: 1.20-1.36) or estradiol was between 400-600 pg/ml (OR 1.44, 95% CI: 1.32-1.57). In a multivariate regression model that included all measured parameters at antagonist initiation, adjusting for age, race, primary diagnosis, and clinic, maximum follicle diameter 10-15mm (OR 1.11, 95% CI 1.03-1.20), CD5 or 6 (OR 1.29, 95% CI: 1.9-1.39), and estradiol between 400-600 pg/ml (OR 1.32, 95% CI: 1.21-1.45), remained independent, positive predictors of improved CPR. CONCLUSIONS: Cycle day, estradiol levels, and maximum follicle size at antagonist start are all independent predictors of egg yield and CPR. The strongest predictor of CPR was antagonist initiation at estradiol level between 400-600pg/ml, followed by CD 5 or 6, and maximum follicle diameter between 10-15mm. P-164 Tuesday, October 18, 2016 PILOT CLINICAL STUDY TO PREDICT IVF OUTCOMES USING EMBRYO MECHANICAL PARAMETERS. L. Z. Yanez,a O. Sedan,b V. L. Baker,b B. Behr,b D. B. Camarillo.a aBioengineering, Stanford University, Stanford, CA; bDepartment of Obstetrics and Gynecology, Stanford University, Palo Alto, CA. OBJECTIVE: To characterize mechanical properties of human embryos after IVF and correlate them with developmental outcomes. DESIGN: We are conducting an ongoing prospective, observational clinical study on patients who are undergoing IVF at Lucille Packard Children’s Hospital (LPCH), have at least 5 oocytes retrieved, and will undergo single embryo transfer. We measure the mechanical parameters of all fertilized embryos at the 2PN stage and record outcomes such as day 3 morphology, day 5/ 6 morphology, preimplantation genetic screening (PGS) results (if available), hCG levels after transfer and pregnancy ultrasound results. MATERIALS AND METHODS: In our previous research, we developed a quantitative and noninvasive method to measure an embryo’s mechanical parameters by observing its response to a negative pressure applied through a micropipette. We have applied machine learning methods to construct a classifier which can assign a viability score to an embryo based on its mechanical parameters at the 2PN stage. The effectiveness of our classifier in predicting a given outcome (such as blastocyst formation or pregnancy) is quantified based on the area under the ROC curve which is calculated using 10-fold cross-validation on our data. RESULTS: So far we have recruited 22 patients, and measured 150 embryos which have resulted in 6 single embryo transfers. The measurement itself did not affect blastocyst formation rates so we believe it to be safe. We found that the fertilization method can affect embryo mechanical parameters, so that intra-cytoplasmic sperm injection (ICSI) results in stiffer, less viscous embryos compared to conventional IVF. We found that 2PN embryo mechanics can predict blastocyst formation with an area under the ROC curve of 0.86 and 0.85 in embryos fertilized via IVF or ICSI, respectively. We also found that 2PN embryo mechanics can predict blastocyst formation better than day 3 morphology, and are not correlated with PGS results at the blastocyst stage. Although our pregnancy data set is small and we are continuing to recruit, in our preliminary data embryos which resulted in positive pregnancy ultrasounds had higher viability scores than those which did not. CONCLUSIONS: Measuring embryo mechanical parameters could be a valuable addition to existing embryo viability assessments. References: 1. L Z Yanez, J Han, B R Behr, R A Reijo Pera, D B Camarillo. ‘‘Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.’’ Nature Communications 7, 2016. Supported by: SPECTRUM pilot grant from Stanford University. P-165 Tuesday, October 18, 2016 IMPACT OF OVARIAN AGING ON PERINATAL OUTCOMES: ANALYSIS OF 135,252 ART CYCLES REPORTED TO SART. M. G. Vega,a S. Zaghi,b S. K. Jindal,c E. Buyuk,d B. Yu.e aDepartment of Obstetrics & Gynecology & Women’s Health, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY; bAlbert Einstein College of Medicine, Bronx, NY; cObGyn and Women’s Health, Montefiore’s Institute for Reproductive Medicine and Health, Hartsdale, NY; d Albert Einstein College of Medicine / Montefiore M, Bronx, NY; eOBGYN, University of Washington, Seattle, WA.

FERTILITY & STERILITYÒ

OBJECTIVE: To determine the relationship between ovarian aging and perinatal outcomes by comparing the outcomes from Assisted Reproductive Technologies (ART) cycles in patients with advance reproductive age using autologous oocytes versus those in the same age group using donor oocytes. DESIGN: Population-based retrospective cohort study of cycles from the SART CORS database. MATERIALS AND METHODS: ART cycles in women 40-43 years old between 2009 and 2013 were assessed. Only cycles with fresh embryo transfers were included. Cycles missing birth weight or gestational age at delivery were excluded. Live birth was defined as birth R 24 weeks gestational age and R500g at birth. Preterm birth was defined as live birth < 37 weeks. The primary outcome was preterm singleton live birth rate. Mann-Whitney U test, Chi-square test, Student t-test, and logistic regression were used for statistical analysis. Age, BMI, prior preterm birth, smoking, uterine factor infertility and ethnicity were controlled for. RESULTS: Among 135, 252 ART cycles, 10263 autologous live births and 8248 donor live births were included. As expected, autologous cycles had a higher miscarriage rate than donor cycles. Surprisingly, autologous cycles resulted in a lower singleton preterm live birth rate when compared to donor oocyte cycles. No significant difference was observed in low birth weight (LBW) at term (<2500g) or intrauterine fetal demise (IUFD) rates between both groups (Table 1). CONCLUSIONS: In women with advanced reproductive age, autologous oocyte cycles resulted in higher miscarriage rate and yet lower preterm birth rate, compared to donor oocyte cycles. This suggests that the negative impact of oocyte aging on fetal survival or perinatal outcomes is minimal beyond early gestational age.

Table 1

Autologous Cycles

Donor Cycles

p value

Preterm birth 1235/10125 (12.2%) 1424/8185 (17.4%) p <0.001 Miscarriage 6912/19389 (35.7%) 2275/14493 (15.7%) p <0.001 IUFD 74/17315 (0.4%) 60/10627 (0.6%) 0.1 LBW 303/8910 (3.4%) 198/6743 (2.9%) 0.1

P-166 Tuesday, October 18, 2016 RISKS OF ADVERSE PREGNANCY AND BIRTH OUTCOMES BY PLURALITY AND MATERNAL FERTILITY STATUS. B. Luke,a D. Gopal,b H. Diop,c J. E. Stern.d aObstetrics, Gynecology, and Reproductive Biology, Michigan State University, East Lansing, MI; bBoston University School of Public Health, Boston, MA; cMass Department of Public Health, Boston, MA; dObstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Lebanon, NH. OBJECTIVE: To evaluate the effect of maternal fertility status on the risk of pregnancy and birth complications by plurality. DESIGN: Longitudinal cohort study, linking cycles from the SART CORS, hospital discharge, and vital records from 2004-10 in Massachusetts. MATERIALS AND METHODS: The study included three fertility groups: women without ART or other infertility treatment (fertile); women with indicators of subfertility but no ART treatment (subfertile), and women with ART treatment. The risks of six adverse outcomes were modeled by plurality using logistic regression, adjusted for parental ages, race/ethnicity, education, payor status, maternal pre-existing conditions (diabetes and chronic hypertension), and infant gender(s). Adjusted odds ratios (AORs) and 95% confidence intervals are reported. Fertile women were the reference group. RESULTS: The study population included 451,975 pregnancies: 447,510 fertile, 8,778 subfertile, and 13,687 ART; and 459,623 singletons and 10,352 twins. The risks of adverse pregnancy and birth outcomes by fertility status and plurality are shown below. The risks for all adverse outcomes were significantly increased in the subfertile and ART groups. CONCLUSIONS: The risks for adverse pregnancy and birth outcomes are significantly increased for both subfertile and ART-treated women, even after stratifying by plurality and adjusting for confounding factors. Supported by: NIH grant R01 HD067270.

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