Discrepant diagnosis rate of array comparative genomic hybridization in thawed euploid blastocysts

• Published in: Journal of assisted reproduction and genetics Vol. 33; no. 7; pp. 893 - 897
• Main Authors: Tiegs, Ashley W., Hodes-Wertz, Brooke, McCulloh, David H., Munné, Santiago, Grifo, James A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2016; Springer Nature B.V
• Subjects: Biopsy; Birth rate; Blastocyst - cytology; Chromosomes; Cohort Studies; Comparative Genomic Hybridization - methods; Counseling; Diagnostic Errors - statistics & numerical data; Embryo Implantation - physiology; Embryo Transfer - methods; Embryos; Female; Fertility; Fertilization in Vitro; Genetic Testing - methods; Genetics; Gynecology; Human Genetics; Humans; Hybridization; In vitro fertilization; Medicine; Medicine & Public Health; Miscarriage; Ovaries; Pregnancy; Preimplantation Diagnosis - methods; Reproductive Medicine; Retrospective Studies; Treatment Outcome; New York; United States > US; Misdiagnosis; Preimplantation genetic diagnosis (PGS); Preimplantation genetic screening (PGS); Array comparative genomic hybridization (aCGH); Counseling; Error rate
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-016-0695-3

Purpose
Preimplantation genetic screening (PGS) and diagnosis (PGD) with euploid embryo transfer is associated with improved implantation and live birth rates as compared to routine in vitro fertilization. However, misdiagnosis of the embryo is a potential risk. The purpose of this study was to investigate the clinical discrepant diagnosis rate associated with transfer of trophectoderm-biopsied blastocysts deemed to be euploid via array comparative genomic hybridization (aCGH).
Methods
This is a retrospective cohort study including cycles utilizing PGS or PGD with trophectoderm biopsy, aCGH, and euploid embryo transfer at a large university-based fertility center with known birth outcomes from November 2010 through July 2014 (
n
 = 520).
Results
There were 520 embryo transfers of 579 euploid embryos as designated by aCGH. Five discrepant diagnoses were identified. Error rate per embryo transfer cycle was 1.0 %, 0.9 % per embryo transferred, and 1.5 % per pregnancy with a sac. The live birth (LB) error rate was 0.7 % (both sex chromosome errors), and the spontaneous abortion (SAB) error rate was 17.6 % (3/17 products of conception tested, but could range from 3/42 to 7/42). No single gene disorders were mistakenly selected for in any known cases. 
Conclusions
Although aCGH has been shown to be a highly sensitive method of comprehensive chromosome screening, several possible sources of error still exist. While the overall error rate is low, these findings have implications for counseling couples that are contemplating PGS and PGD with aCGH.