The role of aneuploidy in repeated implantation failure: implications for patient counseling and preimplantation genetic screening

Abstract

OBJECTIVE: It has been suggested that the use of preimplantation genetic screening (PGS) to assist in the identification and preferential transfer of chromosomally normal embryos, may lead to improved IVF outcomes for certain groups of patients. Current PGS strategies, employ FISH analysis of 9-12 chromosomes, and have been shown to increase implantation and pregnancy rates for women of advanced age and women with recurrent spontaneous abortion. However, patients with repeated implantation failure (RIF) have been harder to target. We employed comparative genomic hybridization (CGH) clinically, to examine the entire chromosome complement of oocytes and embryos derived from RIF couples. DESIGN: Investigation of all chromosomes in zygotes and blastocysts using CGH. MATERIALS AND METHODS: First and second polar bodies (PBs) were biopsied from 194 zygotes from 27 women (average age: 40 years) and analyzed by CGH. Additionally, 79 blastocysts from 13 women (average age: 37 years) were also biopsied and examined. All patients had a history of failed IVF attempts (mean 3.9 failed cycles). Zygotes and blastocysts were cryopreserved while CGH analysis took place. Normal embryos were transferred in subsequent cycles. RESULTS: The oocyte and blastocyst aneuploidy rates were 68% and 43% respectively. 27% of aneuploid zygotes were classified as highly abnormal (3 or more chromosome errors), versus 16% of blastocysts. PGS using FISH would have failed to detect 42% of oocyte and 38% of blastocyst aneuploidies. Thus far, 12 women have had an embryo transfer (ET) after PB CGH, leading to one ongoing pregnancy. 6 women have had an ET after blastocyst analysis, resulting in 4 ongoing pregnancies. Further ET's are underway. CONCLUSIONS: Comprehensive screening of oocytes and blastocysts revealed that errors may affect any chromosome in material from RIF patients, including unusual types of abnormality not seen during later gestational stages. Screening of oocytes from RIF patients seems to have little if any impact on pregnancy rates, although such analyses may reveal prognostic information (some patients had multiple abnormalities affecting all oocytes and are unlikely to be able to conceive using their own gametes). Unlike oocyte screening, blastocyst analysis was associated with high pregnancy rates. Hence, the application of comprehensive chromosome screening is likely to assist a subset of RIF patients (those capable of producing blastocysts) in achieving pregnancies.