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Preimplantation Genetic Screening For All 24 Chromosomes By Microarray Comparative

Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

ABSTRACT

CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis

INTRODUCTION

The last decade has seen a focused and persistent effort toward developing means and technologies to identify embryos that are most likely to implant and grow till term resulting in the birth of a healthy live baby. At present, morphology evaluation is the mainstay of embryo selection since it is noninvasive and easy to perform. However, it has not proved to be a very efficient method for selecting embryos since implantation rates and clinical pregnancy rates (PR) per transferred embryo continue to be very low. Among many factors, one major reason for poor reproductive potential of embryos generated in vitro is the prevalence of aneuploidies in such embryos. The rate of aneuploidy rises with increasing maternal age] but it is only moderately associated with morphology. Therefore, a significant percentage of even the “most ideal” embryos selected for transfer will be aneuploid, resulting in poor reproductive outcome. Moreover, transferring aneuploid embryos can be potentially dangerous since aneuploidy is the most common cause of miscarriage and the most common genetic abnormality in embryos. Preimplantation genetic screening (PGS), even though highly invasive in nature, started out as a very promising concept allowing embryos to be screened for aneuploidies before being selected for transfer. However, this older version of PGS failed to live up to expectations, as numerous authors failed to show improvement in in vitro fertilization (IVF) outcomes with PGS using fluorescence in situ hybridization (FISH), in which chromosomal analysis of not all but only a few chromosomes was performed. With the advent of new validated platforms for comprehensive chromosomal screening (CCS) such as single nucleotide polymorphism array, microarray comparative genomic hybridization (array CGH), and quantitative polymerase chain reaction (PCR), capable of analyzing all 24 chromosomes, now an improved version of PGS involving 24 chromosome copy number analysis is being expected to be a likely remedy for the earlier shortcomings. This retrospective case–control study seeks to examine the efficacy of PGS applied to poor prognosis patients, given the relative paucity of information concerning the use of modern 24 chromosome copy number analysis for this patient group. The objectives of this study were to establish the incidence of aneuploidy in such patients undergoing IVF with poor prognosis and to undertake a retrospective comparative analysis of the clinical outcomes of these patients undergoing IVF PGS cycles with non PGS, IVF controls.



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