Sustained implantation rate is not impacted by increasing fragile X premutation allele size

P-487 Wednesday, November 1, 2017 SUSTAINED IMPLANTATION RATE IS NOT IMPACTED BY INCREASING FRAGILE X PREMUTAC. Jalas,a TION ALLELE SIZE. J. L. Bedard,a C. R. Juneau,b R. S. Zimmerman,a R. T. Scott, Jr.,b aFEC, Basking Ridge, NJ; bIVI/RMA, Basking Ridge, NJ. OBJECTIVE: Fragile X (FX) premutation carrier patients are at risk for premature ovarian insufficiency (POI), which hinder the effects of IVF. Recent work demonstrated that FX associated embryology is comparable to controls. The questions that remain are 1) how many patients that present for FX PGD have at least one embryo suitable for transfer, and 2) is the sustained implantation rate (SIR) lower for embryos created from a FX premutation carrier? DESIGN: Retrospective Observational Study. MATERIALS AND METHODS: Patients from March 2011 to April 2017 from a single IVF center who underwent PGD for FX (with concurrent qPCRbased aneuploidy screening) were included. PGD was performed by a single laboratory that utilized qPCR-based SNP genotyping for linkage analysis. This method determines which embryos inherited the FX-positive maternal chromosome, but cannot determine the size of the CGG repeat in the embryo. Patient characteristics, PGD results, and clinical outcomes including SIR (defined as presence of fetal cardiac activity at 8 weeks of pregnancy/ the number of embryos transferred) were analyzed. Embryos were considered available for transfer if they were euploid and negative for the FX affected haplotype. RESULTS: 28 patients had probes developed for FX PGD and underwent a total of 49 attempted IVF cycles were included. The mean patient age was 31.7
4.8 years. The average CGG repeat size was 100.3 repeats, including 1 full mutation. Due to poor response, 1 patient did not proceed; resulting in 27 patients undergoing a retrieval. 24 patients produced viable blastocysts to undergo PGD. 21 patients had 68 embryos available for transfer, with only 3 patients not producing normal blastocysts. While 4 patients are awaiting their transfer cycles, 17 patients underwent a single embryo transfer. A total of 21 embryos were transferred. 15 patients experienced a successful implantation, yielding 18 ongoing pregnancies. The median number of cycles that a patient underwent was 1.7 cycles. 12 patients only needed 1 cycle to have a successful transfer. The euploid rate per cycle was 68.9%, as expected in this young patient cohort. The SIR for a patient’s first transfer was 88.2%, and overall the SIR was 85.7%. These numbers also suggest that the SIR does not negatively correlate with an increasing maternal premutation allele size, although more patients are needed to fully investigate. Maternal CGG Repeat Size

45-55

56-79

80-99

R100

Number of patients 2 12 8 6 who started at least one IVF cycle % Patients with 100% (2/2) 82% (9/11) 100% (5/5) 83% (5/6) at least one usable embryo Average sustained 100% (1/1) 63% (5/8) 100% (4/4) 100% (4/4) implantation rate (%)

CONCLUSIONS: Nearly all patients presenting for PGD for FX were successful in achieving at least one sustained pregnancy. To our knowledge these data are the largest cohort to date of patients undergoing PGD for FX that includes clinical outcomes. P-488 Wednesday, November 1, 2017 A RETROSPECTIVE CHART REVIEW EXAMINING THE CLINICAL UTILITY OF FAMILY HEALTH J. Russo,a J. L. Garbarini,b HISTORY. K. Dao,a S. C. Johal,c S. Wieloch.d aSarah Lawrence College, Bronxville, NY; bCooperSurgical, Oreland, PA; cRecombine, A CooperSurgical Company, Canal Fulton, OH; dRecombine, Inc, Lansdale, PA. OBJECTIVE: Family health history (FHH) is a simple and cost-effective clinical tool widely used by genetic professionals. Although the value of FHH for assessing personal and familial health and reproductive risk within a prenatal population has been demonstrated in past studies, its utility within a genetic carrier screening population has not been evaluated. The purpose of this study was to examine the utility of FHH as a clinical screening tool and

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explore the general outcomes of full FHH evaluations within an expanded carrier screening (ECS) population. DESIGN: A retrospective chart review was conducted for 500 consults, which included 3-generation pedigrees, using data from the genetic testing company Recombine. MATERIALS AND METHODS: Data from the consult letters were examined to assess the incidence of findings that met criteria for further action. Findings were assigned to 1 of 2 categories: requiring further follow-up, or requiring general risk counseling, which could include risk assessment and/or patient education. Analysis was done to examine the types of follow-up recommendations that were made and the topics discussed in general risk counseling. Statistical analysis included calculations of frequency and confidence interval. RESULTS: Of the 182 consults with negative carrier screening results, 114 (28.2% of the total consults) had additional indications in the family histories that warranted recommendations for further follow-up, general risk counseling, or both. The family history evaluations elicited cancer genetic counseling recommendations in 141 consults with either positive or negative carrier screening results, which comprised 28.2% of all consults (95% confidence interval of 3.94%). Autoimmune and psychiatric disorders were the most frequent topics requiring general risk counseling, occurring in 16.8% and 10.0% of all consults (95% confidence interval of 3.28% and 2.62%, respectively). CONCLUSIONS: These findings demonstrate the high clinical utility of FHH and validate its use in healthcare settings. FHH evaluations provide supplemental information to an individual or couple’s ECS results, allowing for more personalized health and reproductive risk assessments. P-489 Wednesday, November 1, 2017 ADVANCED PATERNAL AGE IS ASSOCIATED WITH A DECREASE IN FERTILIZATION RATES AND INCREASE IN BLASTOCYST SEX CHROMOSOME ANEUPLOIDY. A. Bartoli, K. L. Hornberger, A. King, N. Bachman, D. Young, D. Klepacka, W. B. Schoolcraft, M. Katz-Jaffe. Colorado Center for Reproductive Medicine, Lone Tree, CO. OBJECTIVE: Cumulative sperm point mutations with increasing paternal age have been associated with de novo autosomal dominant genetic disorders and adverse post-natal outcomes. However, limited studies with conflicting results have addressed the association between advanced paternal age (APA), embryo competence and fertility. The aim of this study was to examine the impact of APA on embryo development, aneuploidy and subsequent frozen embryo transfer outcomes in IVF cycles that were controlled for significant female factor infertility. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Couples with APA (mean 51.0
5.7 years), no other male factor infertility and no significant female factor infertility (mean 28.0
4.0 years), underwent IVF with ICSI (n¼50 cycles). Normally fertilized embryos were routinely cultured to the blastocyst stage for trophectoderm biopsy and aneuploidy screening prior to vitrification. Standard protocols for a hormone replacement frozen embryo transfer (FET) were employed and pregnancy outcomes recorded. Statistical analysis included Students t-test, Fishers Exact or Chi-Square test where appropriate, with significance at P<0.05. RESULTS: On average 25.3
14.8 oocytes were retrieved and underwent ICSI, with 14.9
7.7 normally fertilized zygotes (60%) observed on day 1 of embryonic development. This is significantly lower than in IVF cycles with young females and non-APA or male factor partners (Control ¼ 82%; p<0.0001). All APA IVF cycles resulted in embryos developing to the blastocyst stage with a mean of 7.6
3.9 transferable quality blastocysts (Grade 3BB or above) biopsied. The aneuploidy rate for APA blastocysts (34.3%) and the good quality blastocyst conversion rate from fertilized zygote (55%) were equivalent to IVF cycles using young females with non-APA or male factor partners. Chromosome error analysis revealed a trend towards an increase in sex chromosome aneuploidies of APA blastocysts (7.2% vs. 4.9% Control; p¼0.15). A total of 47 euploid blastocyst FETs have been performed to date with 30 ongoing clinical pregnancies/deliveries (63.8%) and only 2 miscarriages (6.3%), comparable to non-APA outcomes. CONCLUSIONS: This study further explored the impact of APA and reproductive success, specifically, in relation to embryo competence and IVF outcomes. Fertilization rates were significantly reduced utilizing APA sperm; however, embryo development and overall blastocyst chromosome constitution was not impacted by increasing paternal age. Nevertheless, this is a small study and further investigation is warranted, specifically in light of an increased trend in sex chromosome aneuploidy of APA blastocysts. Understanding the reproductive risk associated with APA is valuable when counseling patients and managing their expectations prior to undergoing infertility treatment.

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