Polar bodies: their biological mystery and clinical meaning

Abstract

The idea that the polar bodies formed during oocyte maturation are nothing other than ‘aborted ova’ was put forward long ago (Mark, 1881). Despite epochal advances in our knowledge of the developmental and cell biology mechanisms underpinning gametogenesis and early development, we still do not understand the function and fate of the polar bodies. We conjecture that extrusion of the first polar body occurs as a by-product of meiotic division, which enables the preovulatory oocyte to jettison redundant chromosomes while retaining sufficient cytoplasmic resources to sustain preimplantation embryo development. And in practical terms, the polar body offers a readily accessible ‘tester’ that can be sampled for diagnostic purposes as a proxy for the primary oocyte. But the meaning and modus operandi of polar bodies remain mysterious. Guided by the aim of MHR to shed light on fundamental mechanisms in reproduction, this themed issue highlights key studies into the biology of polar bodies and their clinical utilization. The polar body as a tool for clinical diagnosis For many years, the genetics of the polar bodies has been tested in clinical IVF cycles, providing an insight into the cytogenetic or mutational status of the corresponding oocytes, and thereby assisting in the identification of gametes capable of producing healthy (mutationfree or euploid) embryos. The use of polar bodies for PGD was pioneered in Chicago by Yury Verlinsky, Anver Kuliev and others. The Chicago group also contributes to this issue of MHR, sharing their unique data, an accumulation of over two decades of work, the World’s largest experience of PGD applied to polar bodies. Almost 1000 PGD cycles are reported, involving diagnosis of 146 different monogenic conditions. The efficacy of the approach is made plain, with 345 healthy children produced and accuracy rates exceeding 99%. While the paper of Kuliev and Rechitsky (2011) has as a primary focus PGD for single gene disorders, the contribution from Elpida Fragouli and colleagues from the University of Oxford concentrates on cytogenetic aspects of the first and second polar bodies. From the early 1990s, for a period of over 15 years, the dominant strategy for assessing the chromosomal complement of material produced during IVF cycles depended on the analysis of blastomeres biopsied from Day 3 embryos. However, controversy over the accuracy of such analysis, due to the presence of chromosomal mosaicism at the cleavage stage, has led to an upsurge in interest in the testing of polar bodies. In theory, this approach allows the cytogenetic status of the corresponding oocyte to be inferred. Given that the majority of chromosomal anomalies present at conception are predicted to originate in the oocyte and that such abnormalities should affect every cell of the resulting embryos (i.e. gamete-derived aneuploidies are non-mosaic), embryo selection based on the cytogenetic analysis of polar bodies would seem to be a logical and potentially useful approach. However, much remains unknown concerning the incidence, variety and origin of chromosomal anomalies in oocytes and their polar bodies. The paper of Fragouli et al. (2011) seeks to fill in some of the most important gaps by describing comprehensive cytogenetic analysis of the first and second polar bodies of over 300 oocytes. This provides unprecedented information concerning the nature of aneuploidy during meiosis I and meiosis II, revealing findings of clinical and biological importance.