Comprehensive chromosome screening (CCS) with vitrification results in improved clinical outcome in women >35 years: a randomized control trial

ORAL SESSION The following six papers are candidates for the ASRM Scientific Program Prize Paper Awards. Six additional candidates will be presented during the Prize Paper Candidates’ Session on Tuesday morning. SCIENTIFIC PROGRAM PRIZE PAPER ORAL ABSTRACT PRESENTATIONS I O-1 Monday, October 22, 2012 11:15 AM COMPREHENSIVE CHROMOSOME SCREENING (CCS) WITH VITRIFICATION RESULTS IN IMPROVED CLINICAL OUTCOME IN WOMEN >35 YEARS: A RANDOMIZED CONTROL TRIAL. W. B. Schoolcraft,a E. Surrey,a D. Minjarez,a R. L. Gustofson,a R. T. Scott, Jr.,b M. G. Katz-Jaffe.a aColorado Center for Reproductive Medicine, Lone Tree, CO; bReproductive Medicine Associates of New Jersey, Morristown, NJ. OBJECTIVE: Chromosome aneuploidy accounts for >70% of first trimester pregnancy loss, with maternal aging being the most significant risk factor. If demonstrated to be effective, the goal of ART should include the transfer of euploid embryos to maximize the potential for a healthy live birth. The objective of this study was to evaluate the clinical efficacy of blastocyst CCS with trophectoderm (TE) biopsy and vitrification in ART candidates of advanced maternal age (AMA). DESIGN: IRB approved randomized control trial. MATERIALS AND METHODS: Infertile patients of maternal age >35 years were computer randomized at oocyte retrieval into either: Group A ¼ Fresh blastocyst transfer with embryos selected by morphology alone (n¼30) or Group B ¼ Frozen blastocyst transfer with only euploid embryos tested by CCS (n¼30). CCS was performed on TE biopsies using SNP microarray and all biopsied blastocysts were vitrified. RESULTS: There were no significant differences between the groups for maternal age (A¼39.72.2, B¼39.21.7 years), D3 FSH (A¼7.32.1, B¼6.82.1mIU/ml), AMH (A¼2.51.8, B¼2.72.1ng/ml) or AFC (A¼16.37.2, B¼20.910.1). 100% survival was observed following vitrification in Group B. Viable implantation rates (positive cardiac activity) (A¼40.9%, B¼60.8%; P<0.05) and the number of blastocysts transferred (A¼2.20.8, B¼1.70.5; P<0.01) were significantly different between the groups. In addition, significantly higher first trimester pregnancy losses were observed in Group A (A¼20%, B¼0%; P<0.05). CONCLUSION: Infertile AMA patients have higher ongoing implantation rates and fewer first trimester pregnancy losses, following a frozen blastocyst transfer with euploid embryos tested by CCS, when compared to routine fresh blastocyst transfer based on embryo morphology alone. Blastocyst CCS significantly increases the likelihood of ART success for AMA patients, which could allow for the realization of routine single blastocyst transfer, typically only recommended for younger good prognosis patients. Supported by: Ferring Pharmaceuticals. O-2 Monday, October 22, 2012 11:30 AM USE OF DEPOT GnRH ANTAGONIST (DEGARELIX) IN THE OVARIAN STIMULATION IN WOMEN WITH PCOS UNDERGOING IVF. A CONTROLLED TRIAL. M. Sbracia F. Scarpellini. CERM, Hungaria IVF, Rome, Italy. OBJECTIVE: In this study we reported the data of a controlled trial comparing in PCOS women depot GnRH antagonist administered the first day of menstrual cycle versus flexible daily GnRH antagonist protocol. DESIGN: Controlled randomized trial. MATERIALS AND METHODS: We selected 40 women with PCOS (according to Rotterdam criteria). The study was reviewed and approved by the Ethical Committee of the Institution. The patients eligible for the study were informed and they signed an informed consents before undergoing to randomization for treatment.. Patients were randomized by a computer generated number sequence. The women of experimental group underwent at the first day of menstrual cycle to a dose of 20mg of Degarelix (Firmagon 80mg, Ferring Denmark), a depot GnRH antagonist. They underwent controlled ovarian hyperstimulation with recFSH 225IU daily (Gonal-f 900, Merck Serono, Italy) from the second through the sixth day of menstrual cycle and after that adjusted according to patients response. The control group underwent to 225IU of recFSH daily (Gonal-f 900, Merck Serono, Italy) for five days and after adjusted according to patient response;

FERTILITY & STERILITYÒ

when estradiol was higher than 300pg(L or the leading follicle R14mm Cetrorelix 0.25mg/die (Cetrotide Merck Serono, Italy)was started. Patients underwent daily ultrasound scan and plasma levels of Estradiol, Progesterone, Androstenedione, Testosterone assessment. When the leading follicle was R 18mm the ovulation was induced by hCG 10.000IU (Gonasi, IBSA) administration. RESULTS: The pregnancy rate in the experimental group was of 65% whereas in the controls 30% (P<0.05). The number of mature oocytes was statistically significant higher in the experimental group (P<0.01), as well as the number of embryos obtained (P<0.05). The frequency of OHSS was lower in the experimental group than in the controls (5% vs 20%; P<0.05). CONCLUSION: The use of a depot GnRH antagonist in patients with PCOS gave interesting and promising results. These findings should be confirmed in larger studies. O-3 Monday, October 22, 2012 11:45 AM GLUT3 AND CASPR5 – NOVEL GENETIC FACTORS IN MALE INFERTILITY. A. W. Pastuszak, C. J. Jorgez, L. I. Lipshultz, D. J. Lamb. Scott Department of Urology, Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX. OBJECTIVE: Many unrecognized genetic causes of male infertility likely exist. Here, we implicate glucose transporter GLUT3 and contactin-associated protein CASPR5 in male fertility. DESIGN: Genetic study comparing infertile and fertile men. MATERIALS AND METHODS: Genomic DNA from 22 men with nonobstructive azoospermia (NOA) and normal Y-chromosome microdeletion and karyotype assays, as well as 4 fertile men, was used for array comparative genomic hybridization (aCGH) to assess copy number variations (CNVs). Candidate fertility genes were selected using CNV frequency and magnitude, as well as gene expression data. CNVs were validated using qPCR and candidate genes sequenced. Immunohistochemical staining of testis sections used available antibodies and standard protocols. RESULTS: Copy number gains on aCGH were identified in GLUT3 in 2/22 and in CASPR5 in 1/22 NOA men and in no controls, and confirmed using qPCR copy number assays (CNAs). CNAs of DNA from 43 infertile men yielded 5 more men with GLUT3 gains, and no men with CASPR5 losses. The frequency of GLUT3 CNVs in the general population is approximately 5%, whereas our gain frequency is 16%. CNVs in CASPR5 occur in 0.002% of the general population and in 2% of our cohort. Sequencing of GLUT3 yielded benign SNPs in exons 2, 6, and 10; no damaging SNPs were identified in CASPR5. Staining of testis from a male with 3 GLUT3 copies and hypospermatogenesis showed cytoplasmic Leydig cell and spermatocyte staining. CONCLUSION: CNVs in GLUT3 and CASPR5 were identified in infertile males. Future work assessing the impact of both genes on fertility-related cellular pathways, as well as animal model studies, will elucidate the roles of these genes in male fertility. Supported by: AUA Foundation Russell Scott, Jr., MD, Resident Research Award (AWP), NIH grants K12 DK0083014 (CJJ, DJL), the Multidisciplinary K12 Urologic Research (KURe) Career Development Program (CJJ, DJL), and P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH (DJL).

O-4 Monday, October 22, 2012 12:00 PM METHOTREXATE OR EXPECTANT MANAGEMENT IN WOMEN WITH ECTOPIC PREGNANCY OR PUL AND LOW SERUM hCG CONCENTRATIONS? A RANDOMIZED CONTROLLED TRIAL. N. M. van Mello, On behalf of the METEX Study Group. Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Noord-Holland, Netherlands. OBJECTIVE: To determine whether expectant management is effective compared to treatment with systemic methotrexate (MTX) in women with an ectopic pregnancy (EP) or pregnancy of unknown location (PUL) with low but plateauing serum hCG concentrations. DESIGN: Multicentre randomized controlled trial. MATERIALS AND METHODS: We included women with an EP and a plateauing serum hCG <1,500 IU/L and women with a PUL and a plateauing serum hCG <2,000 IU/L. Randomization to single dose systemic MTX or expectant management. Women were monitored weekly, in case of an inadequate decline (<15%) of serum hCG after one week systemic MTX was continued or installed. In case of signs of tubal rupture surgery was performed. The

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