Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of U.S. assisted reproductive technology surveillance data, 2011-2012

P-499 Wednesday, October 21, 2015 TROPHECTODERM BLASTOCYST (TE) BIOPSY RESULTS IN HIGHER PREGNANCY RATE, LOWER MULTIPLE RATE, AND FEWER CYCLES TO PREGNANCY IN GESTATIONAL CARRIERS. A. Nasseri,a K. Gleason,a C. Zollinger,a M. Post,a D. Chen,a J. Grifo.b aThe Valley Hospital Fertility Center, paramus, NJ; b The New York University Fertility Center, New York, NY. OBJECTIVE: To determine the usefulness of comprehensive chromosome screeniong (CCS) by TE biopsy in gestational surrogacy DESIGN: Retrospective case control study MATERIALS AND METHODS: Data from all cycles involving nondonor egg embryo transfers to gestational carriers (GC) at our center from April 2008 to January 2015 were reviewed. FDA screening guidelines were adhered to in all cases. Embryos of the intended parents (IP) were created as per routine IVF protocol. There were a total of 88 embryo transfer cycles. Twenty eight cycles involved the transfer of frozen eupolid blastocysts after TE biopsy. Embryos were screened for all 24 chromosomes by array CGH (group A). Of the remaining 60 cycles (group B), there were 35 fresh, and 25 frozen transfers. One fresh transfer was canceled due to embryo arrest. Paired student t-test and the Chi-squared test of independence were used for statistical analysis. P value <0.05 was considered statistically significant. RESULTS: Group A (CCS)

Group B (untested)

29/36 2.9/1.7 2.6/0.5 80% 21% 68% 1.1 5% 10.5%

31/36 2.8/1.2 2.5/0.25 73% 33% 38% * 2.1 * 35% * 21.7%

Age GC/Age IP Gravida GC/Gravida IP Para GC/Para IP Fertilization Rate ICSI Clinical Pregnancy Average No Embryos per ET Multiples SAB

(* p<0.05) There was no difference with respect to age of the GC’s, age of the female IP’s, GC gravida, GC para, IP gravida, and IP para, between groups A and B.. Fertilization rates and the incidence of ICSI were also similar between the two groups. Group A had a significantly higher clinical pregnancy rate compared to group B despite a significantly lower number of embryos transferred in group A. Multiple pregnancy rate was significantly higher in group B. All but one patient in group A received a single embryo at transfer. That patient received 2 embryos which resulted in the sole multiple pregnancy in this group (triplets). Although there were 5 spontaneous losses (SAB) in group B vs only 2 in group A, this difference did not reach statistical significance. On the average, it required 2.6 cycles of embryo transfer to achieve a live born or ongoing pregnancy in group B vs 1.5 cycles in group A.

CONCLUSIONS: Gestational surrogacy is an excellent model for examining embryo competancy. Comprehensive chromosomal screening using TE biopsy is associated with higher pregnancy rates, fewer multiple pregnancies and lower number of cycles necessary to achieve a clinical pregnancy in gestational carriers. Aneuploidy screening using this technique may also prove to be economically favorable to IP’s as it limits the number of embryo transfer cycles necessary to acheive a liveborn. P-500 Wednesday, October 21, 2015 REBIOPSYAND PREIMPLANATION GENETIC SCREENING (PGS) REANALYSIS DEMONSTRATE THE MAJORITY OF ORIGINALLY ‘‘NO DIAGNOSIS’’ EMBRYOS ARE EUPLOID WITH COMPARABLE PREGNANCY RATES. A. Kaing,a L. Kroener,a M. Brower,a D. Hill,b,c H. Danzer,c J. Barritt.b,c aOb/Gyn, University of California, Los Angeles, Los Angeles, CA; bART Reproductive Center, Beverly Hills, CA; cSouthern California Reproductive Center, Beverly Hills, CA. OBJECTIVE: The genetic viability and clinical outcomes of embryos that undergo PGS and do not receive a genetics diagnosis is not clear. We have previously demonstrated that over half of these ‘‘no diagnosis’’ embryos are euploid. The aim of this study is assess the clinical value of these re-biopsied embryos in an expanded cohort.

FERTILITY & STERILITYÒ

DESIGN: Retrospective cohort study from a single large private fertility clinic. MATERIALS AND METHODS: Patients who underwent PGS from January 2010 to February 2015 were analyzed for cycles that resulted in at least 1 embryo without a diagnosis. These cycles were then examined to assess whether embryo re-biopsy was performed. Initial biopsy was performed on either day 3 or day 5, and re-biopsy was performed on either day 5 or day 6. Information on fresh versus frozen re-biopsy, embryo diagnosis, embryo transfer, and pregnancy rate was collected. Fisher’s exact test was used for statistical analysis. RESULTS: There were 1,523 in-vitro fertilization (IVF) cycles with PGS during this time period. Of these cycles, 132 (8.7%) had at least one embryo with ‘‘no diagnosis’’. Overall, there were 183 embryos (2.0%) with ‘‘no diagnosis’’, and 52 (28%) of those embryos underwent re-biopsy. Fortyseven of these embryos were initially biopsied at the blastocyst stage, and 5 were initially biopsied on day 3. At the time of repeat biopsy, 43 of the embryos (83%) were fresh and 9 (17%) had undergone a thaw after initial cryopreservation. Of the 52 embryos that were re-biopsied and reanalyzed, 96% were assigned a genetic diagnosis. There was no difference in the likelihood of obtaining a diagnosis between fresh and cryopreservedthawed re-biopsied embryo (95.3% versus 100%, p¼1.00). Twenty-five re-biopsied embryos were diagnosed as euploid (53%). Fourteen of these chromosomally normal re-biopsied embryos were transferred, and the clinical outcome of eight of these embryos that were replaced as single embryo transfers (SET) could be accurately assessed. The pregnancy rate after SET was 37.5% (3/8) for all re-biopsied embryos, and 60% (3/5) for only initial blastocyst biopsy embryos. CONCLUSIONS: Embryos that have undergone PGS with a ‘‘no diagnosis’’ result can be safely and successfully re-biopsied fresh as well as after cryopreservation and thaw. A chromosomal diagnosis was successfully assigned in 96% of re-biopsied embryos. Over half of these re-biopsied embryos were diagnosed as euploid after re-analysis with aCGH. Although the numbers are small, pregnancy rates after transfer of euploid re-biopsied embryos are comparable to single-biopsied euploid embryo transfer rates in the literature, demonstrating the high clinical utility of these embryos.

P-501 Wednesday, October 21, 2015 OUTCOMES OF IN VITRO FERTILIZATION WITH PREIMPLANTATION GENETIC DIAGNOSIS: AN ANALYSIS OF U.S. ASSISTED REPRODUCTIVE TECHNOLOGY SURVEILLANCE DATA, 20112012. J. Chang, S. Boulet, G. Jeng, L. Flowers, D. Kissin. Centers for Disease Control and Prevention, Atlanta, GA. OBJECTIVE: To assess the characteristics of assisted reproductive technology (ART) cycles for which preimplantation genetic diagnosis (PGD) was used, and to evaluate indications for PGD and treatment outcomes associated with this procedure as compared to cycles without PGD. DESIGN: Retrospective cohort study using data from U.S. fertility clinics reporting to the National ART Surveillance System (NASS). MATERIALS AND METHODS: Data analysis was limited to fresh autologous cycles that took place in clinics that performed at least one PGD procedure in 2011-2012, involved retrieval of at least one oocyte, and resulted in transfer of at least one embryo at blastocyst stage. We used logistic regression models (adjusting for maternal history and clinical information pertaining ART treatment) to evaluate age-specific treatment outcomes (pregnancy, miscarriage, live birth delivery, and multiple birth delivery) among PGD for genetic factors (PGD-Genetic), PGD for aneuploidy screening (PGDAneuploidy), and PGD for other or unknown reasons (PGD-Other) in comparison to non-PGD cycles. RESULTS: Of 106,902 cycles that met the study inclusion criteria, PGD was used in 9,833 cycles. The majority of PGD cycles were performed for aneuploidy screening (55.7%, n¼5,477), followed by other reasons (29.1%, n¼2,861) and genetic testing (15.2%, n¼1,495). Among women <35 years, all types of PGD cycles had lower odds of pregnancy and live birth than non-PGD cycles. For women 35-37 years, the adjusted odds of pregnancy and live birth were lower for PGD-Other cycles compared with non-PGD cycles (aOR¼0.77, 95% CI: 0.64-0.94 and 0.67, 95% CI: 0.550.82, respectively); PGD-Aneuploidy cycles were negatively associated with miscarriage (aOR¼0.62, 95% CI: 0.45-0.86). Among women >37 years, PGD Aneuploidy cycles were positively associated with pregnancy (aOR¼1.20, 95% CI: 1.06-1.36), live birth delivery (aOR¼1.34, 95% CI: 1.18-1.52), and multiple birth delivery (aOR¼1.91, 95% CI: 1.47-2.48) and negatively associated with miscarriage (aOR¼0.51, 95% CI: 0.400.65) compared with non-PGD cycles.

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CONCLUSIONS: Aneuploidy screening was the most common indication for PGD. Use of PGD was not associated with increased rates of pregnancy and live birth for women <35 years, irrespective of the indication. PGD for aneuploidy was associated with lower odds of miscarriage for women aged 35 and older and higher likelihood of having a live birth and a multiple live birth delivery among women >37 years, thereby suggesting that more viable or euploid embryos were transferred after screening. P-502 Wednesday, October 21, 2015 WITHDRAWN P-503 Wednesday, October 21, 2015 ELEVATED SERUM PROGESTERONE REDUCES THE LIKELIHOOD OF LIVE BIRTH AFTER FROZEN TRANSFER OF EUPLOID EMBRYOS: TOO MUCH OF A GOOD THING? L. A. Kondapalli,a L. Munkwitz,a R. Collins,a D. A. Minjarez,b W. B. Schoolcraft,a M. Katz-Jaffe.a aColorado Center for Reproductive Medicine, Lone Tree, CO; bColorado Center for Reproductive Medicine, Denver, CO. OBJECTIVE: Although comprehensive chromosomal screening (CCS) allows for selection of euploid embryos with high implantation and live birth rates, IVF failures still occur. The objective of this study was to investigate factors associated with negative pregnancy after frozen transfer. DESIGN: Case control study MATERIALS AND METHODS: Patients undergoing euploid frozen embryo transfers (FET) between 2013-2014 were included (n¼441). All embryos were biopsied at the blastocyst stage for CCS prior to vitrification. Standard protocols were used for hormone supplementation prior to FET. Patients were stratified by cycle outcome: successful live birth versus non-pregnant (including biochemical pregnancy). Data on demographics, ovarian reserve markers, IVF stimulation, and cycle outcomes were obtained from medical records. Appropriate parametric and non- parametric statistical analyses were performed using STATA version 13.1 (Stata Corp; College Station, TX, USA) with P value <0.05 considered significant. Multivariate logistic regression was used to control for potential confounders. RESULTS: Women who achieved live birth were older at FET, had thicker endometrial contour (EMC) and higher number of embryos transferred compared to non-pregnant women [Table 1]. In contrast, serum progesterone (P4) was significantly higher in the non-pregnant group. After adjusting for age, number of embryos transferred and EMC, the associations between live births and P4 (OR 0.96, 0.95-0.98), and AMH (OR 0.87, 0.79-0.96), remained significant.

P-504 Wednesday, October 21, 2015 PREIMPLANTATION GENETIC SCREENING IS COST EFFECTIVE IN COST PER DELIVERY COMPARED TO ROUTINE IN VITRO FERTILIZATION. B. Hodes-Wertz, D. H. McCulloh, J. Grifo. NYU Langone Medical Center, New York, NY. OBJECTIVE: To assess the cost of in vitro fertilization (IVF) with preimplantation genetic screening (PGS) using array comparative genomic hybridization to routine IVF performed from 2011-2013 DESIGN: Retrospective cost analysis MATERIALS AND METHODS: All IVF cycles with PGS (IVF-PGS) performed from 2011-2013 were compared to all routine IVF cycles and subsequent frozen embryo transfers (IVF-suFET) during that time period. All cycles were included that resulted in an egg retrieval. Donor oocyte cycles were excluded. The following costs were considered: routine IVF cycle with and without embryo transfer, frozen embryo transfer of unscreened and euploid embryos, IVF with PGS (including shipping of specimen, outside laboratory cost to run specimen, and cryopreservation of embryos) with and without transfer, dilation and curettage performed on early pregnancy failure, termination of pregnancy, laparoscopic salpingectomy performed for ectopic pregnancy, livebirth of singleton, twins, and triplets. Costs were calculated per patient, per liveborn, and per delivery for 4 age groups. RESULTS: No. of No. of Multiple Multiple Cost per Cost per IVF-suFET IVF-PGS Gestation Gestation delivery delivery patients patients Rate Rate with with (deliveries) (deliveries) IVF-suFET IVF-PGS IVF-suFET IVF-PGS 85 (47) 35-39 yrs old 473 (263) 40-42 yrs old 381 (123) >42 yrs old 194 (28)

412 (272) 150 (83) 141 (47) 74 (6)

21% 17% 22% 4%

4% 7% 2% 0%

$65,356 $69,751 $102,131 $182,463

$65,278 $66,841 $89,350 $291,907

IVF-PGS was cost effective compared to routine IVF-suFET for all age groups except the >42 year old group. There was two triplet pregnancies in the IVF- suFET group and none in the IVF-PGS group. CONCLUSIONS: IVF-PGS is cost effective compared to routine IVF-suFET up until age 43. In fact, this analysis underestimates the cost savings from PGS in that there are qualitative cost savings that are difficult to measure. Underestimated costs include the cost of cryopreservation of aneuploid embryos and the futile transfer cycle that follows, patient experience with miscarriage and lost treatment time that follows, time spent waiting on pregnancy results after transfer of aneuploid embryos, the costs of multiples requiring prolonged post natal care and the financial and emotional cost of terminating a second trimester chromosomally abnormal pregnancy.

Clinical Factors and CCS-FET Outcomes.

Non-Pregnant (n¼228)

Live Birth (n¼213)

P value

36.3  3.8 37.1  3.8 1.3  0.47 9.8  2.1 940  774 47.1  33.9 7.9  5.4 3.1  3.4 19.7  8.8 11.6  5.9 45.2

37.0  3.6 37.9  3.7 1.6  0.50 10.2  1.8 797 635 24.7  25.8 7.4  2.3 2.3  2.5 20.2  8.4 12.1  5.8 40.2

0.08 0.03 <0.001 0.01 0.07 <0.001 0.76 <0.01 0.50 0.31 0.29

Cycle age FET age # embryos transferred EMC (mm) Serum E2 at FET Serum P4 at FET FSH AMH # eggs retrieved # 2pns Prior uterine surgery (%)

CONCLUSIONS: Successful implantation is dependent upon both the developmental competence of the transferred embryo and endometrial receptivity. P4 plays a critical role in coordinating embryo-endometrium synchrony essential for viable implantation. In our population, the likelihood of live birth after euploid FET was significantly reduced in setting of elevated P4 of the day of transfer. Future studies are essential to identify the optimal P4 level that promotes endometrial receptivity and successful pregnancy.

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ASRM Abstracts

P-505 Wednesday, October 21, 2015 COMBINED PGD AND CCS FROM THE SAME BIOPSY: COMPREHENSIVE ANALYSIS WHILE BYPASSING THE INTRINSIC LIMITS OF WGA. R. Zimmerman,a C. Jalas,b X. Tao,c A. Fedick,a R. T. Scott,d N. R. Treff.e aFoundation for the Assessment and Enhancement of Embryonic Competence, Basking Ridge, NJ; bFoundation for the Assessment and Enhancement of E, Basking Ridge, NJ; cFAEEC, Basking Ridge, NJ; dRMANJ, Rutgers-RWJ, Basking Ridge, NJ; eRMANJ, Rutgers-RWJ, Basking Ridge, NJ. OBJECTIVE: Many methods of comprehensive chromosome screening (CCS) involve whole genome amplification (WGA), making it difficult to obtain reliable PGD data for a single gene disorder (SGD) in parallel. This study presents validation and clinical experience with an alternative approach involving multiplex PCR prior to CCS and SGD analyses. DESIGN: Prospective blinded, and observational. MATERIALS AND METHODS: Patients at risk for transmitting an SGD and relevant family members were used to develop custom primers to target informative loci for the mutation (linked and direct) using SNP array analysis (Affymetrix Inc). TaqMan assays (Life Technologies Inc.) for the SGD informative loci were pooled with previously developed CCS primers for the multiplex PCR used for chromosomal copy number analysis. Aliquots of the PCR reaction were then used as template for TaqMan allelic discrimination for the SGD and copy number analysis for CCS. Phase 1 involved comparison of this PCR based testing from one biopsy against reference lab data

Vol. 104, No. 3, Supplement, September 2015