Pregnancy outcomes between euploid and non-tested blastocysts in frozen embryo transfer cycles

OBJECTIVE: To determine whether iatrogenic factors not related to aneuploidy but to ART practice could impact the chance of miscarriage. DESIGN: This retrospective cohort study included a total of 3,074 cycles of PGS resulting in pregnancy (+sac) from 30 fertility clinics. The cycles were attempted between 2011 and Dec 2015. Centers reporting substantial number of procedure pregnancy follow up were included in the study. MATERIALS AND METHODS: Blastocyst biopsies from cycles performed at multiple fertility clinics were referred to the same reference laboratory for analysis. Genetic analysis was performed by array Comparative Genome Hybridization (aCGH). RESULTS: On average 11% of implanted sacs were lost, either as empty sacs (5%) or clinical losses after a FHB was detected (6%). However, embryo loss per center ranged from as low as 2% (2/89) to as high as 23% (9/61). There were several centers with significantly different embryo loss rates than the mean 11% (p<0.001). One center in particular, had actually an increase in embryo loss frequencies over the years, from 2% (2/89, year 2011-12), to 16% (49/316, 2013-14), to 21% (19/91, 2015), which was significantly different (p<0.001). Maternal age, region, number of embryos with no result (a potential biopsy issue), and indication for PGS (i.e. RPL) were not a factor for these differences. We also compared the miscarriage rate of those centers with their reported loss rate for SART 2014 for frozen transfer, and on average the miscarriage rate weighted by age was 18.45% compared to 11% for PGS. Centers with high PGS miscarriage rates did not have high miscarriage rates in the SART dataset. CONCLUSIONS: The study shows for the first time a strong association between center-specific ART practices and frequency of embryo loss. Being the genetics lab the same and all embryos diagnoses as euploid, this leaves as suspect causes luteal support and blastocyst biopsy techniques as some of the potential causes for these differences. It is paramount to determine these causes since these changes defeat the purpose of PGS, replacing embryos with the highest ongoing implantation potential. One word of caution is; due to the study being retrospective, associations are apparent, and causality cannot be established. Reference: 1. Munne S. Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization. Current Genomics. 2012;13(6):463-470. http://dx.doi.org/10.2174/138920212802510457. P-452 Wednesday, November 1, 2017 LIVE BIRTH RATE IS ASSOCIATED WITH INFERTILITY DIAGNOSIS FOLLOWING FET OF CHROMOSOMALLY EUPLOID BLASTOCYSTS: ANALYSIS OF 5,633 CYCLES REPORTED TO SARTCORS. F. Meng,a,b M. Goldsammler,a,b E. Wantman,c S. K. Jindal.a,b aObGyn and Women’s Health, Montefiore’s Institute for Reproductive Medicine and Health, Hartsdale, NY; b Albert Einstein College of Medicine, Bronx, NY; cRedshift Technologies, Inc., New York, NY. OBJECTIVE: To evaluate euploid embryo competency based on the etiology of the infertility (endometriosis, diminished ovarian reserve, male factor, tubal factor or unexplained/unknown). DESIGN: Retrospective cohort study. MATERIALS AND METHODS: All autologous and donor egg day 5 PGS-FET cycles from 2014 reported to SARTCORS were evaluated. Demographic data including patient age, BMI, smoking, prior fertility and etiology of infertility were collected and analyzed. Exclusion criteria were patients with uterine abnormalities, PGD cycles for single gene disorders, gender selection or HLA determination. The outcome measure was live birth rate. STATA v14.2 was used to perform statistical analysis including X2 test. Lo-

gistic regression models were created to control confounding variables such as age, smoking, prior fertility, and max FSH values. P<0.05 was considered statistically significant. RESULTS: Live birth rates following PGS-FET of euploid embryos were 58% for both autologous and donor oocytes. A diagnosis of unexplained or unknown cause infertility was associated with significantly higher live birth rates following FET of euploid embryo even after controlling for confounding variables [OR 1.27 (95% CI 1.05- 1.55), p¼0.02]. Diminished ovarian reserve conferred a significantly lower live birth rate than other infertility diagnoses on unadjusted analysis and continued to show an association with lower live birth rates following adjusted analysis [OR 0.81 (95% CI 0.651.01), p¼0.07)]. CONCLUSIONS: Unexplained infertility is associated with a higher live birth rate compared to patients with known etiology infertility. Diminished ovarian reserve is associated with lower live birth rates, despite chromosomally euploid embryos. We postulate that once euploid embryo competency is established in patients with unexplained infertility, their pregnancy outcomes are significantly improved. Further studies are being conducted to determine associations with patient age and secondary outcome measures. P-453 Wednesday, November 1, 2017 PREGNANCY OUTCOMES BETWEEN EUPLOID AND NON-TESTED BLASTOCYSTS IN FROZEN EMBRYO TRANSFER CYCLES. J. Thorne, L. A. Kaye, A. Bartolucci, C. A. Benadiva, J. Nulsen, L. Engmann. Dept. of Reproductive Endocrinology & Infertility, University of Connecticut Health Center, Farmington, CT. OBJECTIVE: Debate continues on the clinical value of preimplantation genetic screening (PGS) and whom it may benefit. We compared pregnancy outcomes in frozen embryo transfer (FET) cycles between non-tested blastocyst transfers immediately following a freeze-all in vitro fertilization (IVF) cycle and euploid blastocyst FET cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 279 cycles performed at a large university-based center during a four-year period were evaluated. 116 blastocyst FET cycles subsequently following a freeze-all IVF cycle and 163 euploid blastocyst FET cycles were included for analysis. The primary outcome was ongoing pregnancy rate (OPR). Secondary outcomes included implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple pregnancy rate (MPR). Patients were further stratified by age and number of embryos transferred. Student’s t-test was used to assess continuous variables. Chi-square and Fisher’s exact test was used to assess categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value <0.05 was considered statistically significant. RESULTS: Among all patients, IR (67.2% vs. 71.5%, p¼0.45), CPR (76.7% vs. 72.4%, p¼0.42), OPR (61.2% vs. 63.8%, p¼0.66) and CLR (20.2% vs. 11.8%, p¼0.09) were similar between the two groups. Those in the non-tested FET group demonstrated an increased MPR (29.2% vs. 16.2%, p¼0.02); however, this was no longer appreciated in patients receiving a single embryo transfer (2.5% vs 3.4%, p ¼ 0.80). Outcomes were stratified by age (Table). Using logistic regression to control for significant confounding variables of age, BMI, and endometrial preparation protocol, the adjusted odds ratio for OPR was 0.77 (95% CI 0.46-1.30, p¼0.33). CONCLUSIONS: PGS improves pregnancy and clinical loss rates in an older patient population. Women under 35 years utilizing PGS had decreased multiple pregnancy rates; however, if a single blastocyst transfer was performed there was no benefit to testing embryos.

Pregnancy Outcomes Stratifed by Age

<35 PGS <35 Untested 36-37 PGS 36-37 Untested 38-40 PGS 38-40 Untested 41-42 PGS 41-42 Untested Bold: p<0.05

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IR, n (%)

CPR, n (%)

OPR, n (%)

CLR, n (%)

62/85 (72.9) 79/104 (76.0) 30/44 (68.2) 21/40 (52.5) 37/45 (82.2) 13/21 (61.9) 10/16 (62.5) 3/10 (30.0)

55/75 (73.3) 62/75 (82.7) 25/36 (69.4) 13/23 (56.5) 26/32 (81.3) 11/12 (91.7) 10/14 (71.4) 3/5 (60.0)

46/75 (61.3) 54/75 (72.0) 24/36 (66.7) 10/23 (43.5) 25/32 (78.1) 7/12 (58.3) 7/14 (50.0) 0/5 (0.0)

9/55 (16.3) 7/62 (11.2) 1/25 (4.0) 3/13 (23.1) 1/26 (3.8) 4/11 (36.3) 3/10 (30.0) 3/3 (0.0)

ASRM Abstracts

MPR, n (%) 5/55 (9.1) 17/62 (27.4) 4/25 (16.0) 6/13 (46.2) 10/26 (38.5) 3/11 (27.3) 0/10 (0.0) 0/3 (0.0)

Vol. 108, No. 3, Supplement, September 2017