Fertilization : In Vitro Assessment of 19,803 Paired Chromosomes and Clinical Outcome from First 150 Cycles using Array CGH of the First Polar Body for Embryo Selection and Transfer

Background: Meiosis 1 errors are believed to be the largest single cause of clinical embryo failure and early miscarriage. Following the failure of FISH technology and concerns over embryo mosaicism, our aim was to assess paired chromosome status and error rates, and predict oocyte aneuploidy using the metaphase2 polar body with a novel arrayCGH platform as a means to select embryos for couples with multiple IVF failures. Methods: The PB1 was removed from metaphase 2 oocytes using a laser-assisted breech of the zona pellucida to effect the biopsy. Reliable 23-paired chromosome analysis was obtained, and in time for fresh embryo transfer. It was a nonrandomised investigation in patients seeking this technology as a result of previous multiples failures of IVF. Results: 134 couples presented for 150 cycles of array CGH with a median age of 41.0. 861 polar bodies were evaluated, 67.4% and 32.6% were aneuploid and euploid, respectively. 19,803 paired chromosomes were analysed, 3.5% and 3.4% of chromosome errors resulted in either a gain or loss, respectively. There was a positive correlation between female age and aneuploidy, but no correlation with numbers oocytes harvested. 26% of cycles (n=39) failed to achieve embryo transfer (ET) as none of the oocytes were euploid. The live birth rate per ET and implantation was 24.1% and 27.7%, respectively, and 5.2% of chemical pregnancies (1.9% of transfers) resulted in a dizygotic multiple pregnancy. Conclusion: Array CGH was proven to generate robust chromosome information. Chromosome segregation error rates were found to be inversely proportional to chromosome length and proportional to the G/C base content. Clinically, the transfer of a single embryo after PB 1 array CGH analysis appeared to generate improved implantation rates in women with very poor prognosis, whilst reducing the risk of a multiple pregnancy. *Corresponding author: Simon Fishel, CARE Fertility Group, John Webster House, 6, Lawrence Drive, Nottingham Business Park, Nottingham, NG8 6PZ, UK. E-mail: simon.fishel@carefertility.com Received October 07, 2011; Accepted November 07, 2011; Published November 29, 2011 Citation: Fishel S, Craig A, Lynch C, Dowell K, Ndukwe G, et al. (2011) Assessment of 19,803 Paired Chromosomes and Clinical Outcome from First 150 Cycles using Array CGH of the First Polar Body for Embryo Selection and Transfer. J Fertiliz In Vitro 1:101. doi:10.4172/2165-7491.1000101 Copyright: © 2011 Fishel S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Aneuploidy is the main cause of miscarriage and congenital birth defects, and is the most common chromosome abnormality in humans with at least 5% of all clinical pregnancies being of trisomy or monosomy origin [1]. Clinical assessment of in vivo conceived pregnancies over five decades has catalogued risk factors and aetiology in detail, with most apparently derived from errors in maternal meiosis 1 [1]. An IVF cycle, however, generates oocytes and products of conception – the zygote and preimplantation embryo – in far greater numbers than ovulation during the menstrual cycle, and it is believed that the incidence of aneuploidy after ovulation induction for IVF can be up to 50% of oocytes harvested [2,3]. We are beginning to understand, through full chromosome copy number analysis, that anomalies related to embryos of poor ‘quality’, arrested embryos and transferred embryos that do not implant or result in a failed pregnancy, encompass a large and much broader range of aneuploidies than observed in the products of natural conception [4,5]. Preimplantation genetic screening (PGS) procedures using FISH (fluorescent in situ hybridization) are now regarded as redundant for improving live birth rates [6,7]. But, as the prevailing assumption remained that the presence of chromosomal anomalies are a major cause of embryo failure, of which the majority derive from the oocyte there was a need to develop a reliable technology to identify full chromosome copy number. This technology needed to provide dependable data within 48 h to support ‘fresh’ embryo transfer. With such technology meiotic errors (polar bodies 1 and 2), and errors in the embryo resulting from sperm aneuploidy or cleavage mitotic errors can be examined with confidence. In 2008 we were the first to undertake a study to assess the use of a new, robust and reproducible array CGH method to assess full 23 chromosome pair copy number and, when satisfied, applied this approach clinically in ‘last resort’ cases requesting this technology [8]. This approach of PB chromosome assessment by array CGH was subsequently supported by the European Society for Human Reproduction (ESHRE) consortium [9]. Encouraged by the outcome of the technology and its prospects as an objective prognosticator for embryo viability we expanded its clinical use and present the outcome of our experience to date. Materials and Methods