Oocyte and Embryo Selection in Assisted Reproductive Treatments: Methods Improving Outcome and Illuminating Aspects of Meiosis and Embryogenesis.

Abstract

Listen

Translate article

The introduction of in vitro fertilization (IVF) treatment over thirty years ago revolutionized the treatment of infertility and has led to the birth of more than five million babies worldwide. However, this remarkable success masks the fact that IVF treatment remains remarkably inefficient. It is still the case that most patients require more than one cycle of treatment to obtain a viable pregnancy and more than 80% of embryos transferred to the uterus fail to produce a birth. The poor success rate per embryo transferred is a consequence of the extreme variability in the competence of the oocytes and embryos produced during a typical IVF cycle, coupled with the inability of routine morphological evaluations to correctly identify the embryos having the greatest developmental potential. Innovations in genetic testing and embryo culture have recently become available, which may finally allow an accurate evaluation of embryo competence and offer the hope of significant improvements to IVF treatment. These new technologies are also shedding light on important aspects of human oogenesis and preimplantation development. Principal amongst the new methods for embryo selection are those that allow accurate screening for chromosome abnormalities. Aneuploidy is extremely common in human oocytes and embryos and is of great clinical significance, having responsibility for the majority of miscarriages and many instances of congenital abnormality and mental retardation. The application of comprehensive chromosome screening techniques has provided an insight into the frequency of aneuploidy affecting each chromosome. It has been confirmed that during female meiosis errors involving single chromatids are far more common than those affecting whole chromosomes. Lagging of chromosomes during anaphase and failure of chromosomes to migrate to the spindle both occur frequently, contributing to a preponderance of chromosome losses over gains in the polar bodies tested. It has long been known that female meiosis I is the source of most aneuploidies detected during pregnancy and that the incidence of abnormalities increases with advancing age. Data from the comprehensive chromosome screening of polar bodies confirms this to be true for younger patients. However, it is now clear that errors occurring in meiosis II increase more rapidly with advancing age than those derived from meiosis I, such that errors from the second meiotic division predominate for women over 40 years of age. Data from embryos has also provided an interesting insight into chromosome segregation during preimplantation development, confirming a remarkable level of genetic instability characterized by a high frequency of chromosomal malsegregation, mosaicism and chromosome breakage. Clinically, there is rapidly accumulating data showing that IVF outcomes (pregnancy and miscarriage rates) can be significantly improved by testing embryos for aneuploidy and transferring those found to be chromosomally normal, provided appropriate technologies are used.This lecture will review data from more than 2000 human oocytes and embryos tested in our laboratory, providing unique and sometimes unexpected information concerning the mechanisms leading to aneuploidy.