Preimplantation genetic diagnosis (PGD) for single gene defects (SGD): the significant value of concurrent aneuploidy screening

O-198 Wednesday, October 21, 2015 12:30 PM PREIMPLANTATION GENETIC DIAGNOSIS (PGD) FOR SINGLE GENE DEFECTS (SGD): THE SIGNIFICANT VALUE OF CONCURRENT ANEUPLOIDY SCREENING. T. G. Nazem,a K. N. Goldman,a A. S. Berkeley,a J. Grifo.b aNYU School of Medicine, New York, NY; b NYU Langone Medical Center, New York, NY. OBJECTIVE: To evaluate outcome differences between patients undergoing trophectoderm (TE) biopsy and PGD for SGD with and without 24-chromosome aneuploidy screening. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients undergoing their first cycle of blastocyst culture, TE biopsy, and PGD with and without aneuploidy screening (array comparative genomic hybridization, aCGH) from July 2010 to August 2014 were included. Cycles were excluded if performed for gender selection, HLA matching, or translocation. Primary outcomes included number (no.) and percentage (%) of blastocysts affected/unaffected/carrier of SGD, aneuploid/ euploid blastocysts, and blastocysts eligible for transfer. FET cycle outcomes were analyzed: implantation rate (IR), spontaneous abortion rate (SABR), and live birth rate (LBR). Data were analyzed using student’s t-test and Fisher’s exact t-test and presented as mean
S.D. (p< .05). RESULTS: 58 patients met inclusion criteria: 10 patients underwent TE biopsy/PGD, 48 patients pursued TE biopsy/PGD/aCGH. Baseline characteristics were similar in both groups. No. of blastocysts unaffected or carrier of SGD did not differ (45.3% vs. 54.9%, p¼0.6). No. of blastocysts eligible for transfer based on testing performed was significantly lower in the PGD/ aCGH group (2
2.3 vs. 3.8
2.8, p< .05) and % of blastocysts available for transfer was lower (27.4% vs. 59.4%, p< .05), as 17% of blastocysts ‘unaffected’ by SGD were also aneuploid and therefore ineligible for transfer. FET outcomes suggest higher IR and LB rates and lower SAB rates (NS) in the screened group despite transfer of significantly fewer embryos. 58.3% of patients in the PGD/aCGH group had at least one SGD-unaffected embryo that was aneuploid, and thus may have unknowingly transferred an aneuploid embryo without dual-screening [table 1]. CONCLUSIONS: Despite a young mean patient age, over 50% of blastocysts tested for SGD with aCGH were aneuploid. Without concurrent aneuploidy screening, a large number of SGD ‘unaffected’ but aneuploid embryos will be transferred. SABR was higher and LBR was lower (NS) despite transfer of twice as many embryos in the unscreened group. Performing 24-chromosome aneuploidy screening with PGD significantly increases utilization of single ET, an intervention that can drastically improve maternal and neonatal outcomes.

Table 1

Age (y) Day 2 FSH No. oocytes No. 2PN zygotes Total blastocysts Total blastocysts biopsied Mean No. ET % Single ET IR SABR LBR

PGD/aCGH (n¼48)

PGD (n¼10)

P value

32.5
5.9 6.9
8.3 18.7
10.7 12.0
7.4 8.7
5.9 (362) 7.5
5.3

34.4
4.6 5.5
2.5 20.5
6.7 14
5.6 8.2
3.9 (64) 6.4
3

0.3 0.6 0.6 0.4 0.8 0.5

1.1
0.3 85.3% 73% 17.4% 55.9%

1.9
0.6 25% 53.3% 40% 37.5%

< .01 < .05 0.2 0.3 0.4

MALE REPRODUCTION AND UROLOGY: CLINICAL 3 O-199 Wednesday, October 21, 2015 11:15 AM TESTICULAR VEIN SIZE AS MEASURED BY SCROTAL ULTRASONOGRAPHY IS INDEPENDENTLY PREDICTIVE OF VARICOCELECTOMY OUTCOMES FOR MEN WITH CLINICAL GRADE D. G. Dhanjani,a 1 AND 2 VARICOCELES. J. M. Bieniek,a b a a M. K. Samplaski, E. D. Grober, K. C. Lo, K. A. Jarvi.a aUniversity of Toronto, Toronto, ON, Canada; bUniversity of Southern California, Los Angeles, CA.

FERTILITY & STERILITYÒ

OBJECTIVE: Scrotal ultrasonography is a sensitive test for detection of varicoceles however there is controversy over its role in the evaluation and management of male infertility patients. This study aims to determine if ultrasound-measured testicular vein sizes correlate with physical exam findings and ultimately predict results following varicocelectomy. DESIGN: Retrospective review of preoperative scrotal ultrasounds for patients undergoing varicocelectomy with correlation to clinical varicocele grading and post-operative outcomes. MATERIALS AND METHODS: Clinical data for patients presenting to an infertility clinic was collected in an institutional review board-approved database. A review of patients undergoing varicocele surgical repair or embolization from 2003-2012 was performed. Measures of testicular vein size before and after Valsalva maneuver were extracted from available scrotal ultrasound reports. Descriptive statistics were performed on the collated data with Student’s t tests, ANOVA, and Spearman’s rank correlation utilized as appropriate with p< .05 reported as significant. RESULTS: Of 302 patients undergoing varicocelectomy, semen parameters and scrotal ultrasounds were available for 276 patients (91.4%) with a mean age of 40.1 (range 23-68). Clinical grades 1, 2, and 3 left varicoceles were reported in 104 (35.2%), 123 (41.7%), and 67 (22.7%) men, respectively, with solitary left and bilateral varicoceles noted in 113 (40.9%) and 157 (56.9%). Mean post-Valsalva left testicular vein diameter was 4.1mm (IQR 3.5-4.5) and right was 3.8mm (IQR 3.1-4.2). Vein size was significantly different between grades 1, 2, and 3 left varicoceles (p< .001) but did not differ significantly for right grades (p¼ .08). Amongst men with grade 1 or 2 left varicoceles, those with vein size >3.5mm had an average 3.13 fold change in TMC post-operatively versus 1.79 if veins <3.5mm (p¼ .04). For all varicocele grades, a positive correlation was noted between maximal left vein diameter and change in motility (r¼.12, p¼ .04) but neither left nor right vein diameter had significant correlations with sperm concentrations, total motile count (TMC), or change in TMC. CONCLUSIONS: For men with grade 1 or 2 varicoceles by physical examination, testicular vein size as measured by scrotal ultrasound is independently predictive of post-varicocelectomy outcomes. Men with larger veins measured by ultrasound had close to a 75% greater fold increase in TMC than those with small veins. O-200 Wednesday, October 21, 2015 11:30 AM DOES PATERNAL AGE HAVE AN EFFECT ON TOTAL MOTILE SPERM COUNTS (TMC) AND THE OUTCOME OF OVULATION INDUCTION/INTRAUTERINE INSEMINATION (OI/IUI) CYCLES? I. Dimitriadis,a G. Murtadi,b T. L. Toth,c I. Souter.d aTufts b Medical Center, Boston, MA; Massachusetts General Hospital Fertility Center, Boston, MA; cMassachusetts General Hospital, Boston, MA; dHarvard Medical School-Massachusetts General Hospital, Boston, MA. OBJECTIVE: To evaluate whether paternal age affects IUI prepared postprocessing TMC and thus the outcome of OI/IUI cycles. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Setting: Academic fertility center. Patients/Interventions: Data from 4,299 OI/IUI cycles from 1,808 patients were analyzed to evaluate the association between paternal age and TMC. In addition, a subgroup of women <38 years was identified and cycle outcomes from those with male partners <40 years were compared to those with partners R40 years. Outcome measures: TMC, clinical pregnancy (CPR) and spontaneous abortion (SABR) rates.Statistics: Pearson correlation, t-test and x2 were used as appropriate. RESULTS: When all patients were included in the analysis, a statistically significant negative correlation was found between paternal age and mean TMC (r:-0.08; p¼0.0005). When restricting the analysis to a subgroup of women <38 years (N¼1,283), we noted significantly lower TMC and higher rates of male factor infertility (MFI) among male partners R40 as compared to those <40 years (mean
SD TMC: 38.1
47.4 vs. 50.0
57.3 million; p<0.0001; and MFI: 22.5% vs. 11.1%, p¼0.0002; for males R40 vs. <40 years, respectively). However, despite the lower TMC noted among males R40 years, as compared to those <40 years, CPR and SABR were comparable (CPR: 14.2% vs. 12.7%, p¼0.41; 20.3% vs. 12.6%, p¼0.15; respectively), albeit a more favorable maternal age among male partners <40 years (34.5
2.5 vs. 32.5
3.0 years, p<0.01, for patients with male partners R40 vs. <40 years, respectively). Groups did not differ otherwise in day-3 FSH, maternal BMI, or type of OI treatment. CONCLUSIONS: Advancing paternal age negatively affects post-processing TMC. In a population of younger women though, the negative effect of paternal age on TMC, did not significantly affect the outcome of OI/IUI cycles.

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