Polar body diagnosis of 263 unfertilised oocytes: Frequent finding of aneuploidies

Introduction: Aneuploidies of human oocytes are presumed to be a major cause of fertilisation failure in assisted reproductive treatment (ART) cycles. As underlying mechanisms of origin, meiotic nondisjunction of bivalent chromosomes as well as unbalanced predivision of chromatids are discussed [1,2]. The purpose of this study was to evaluate the frequency of aneuploidies in oocytes remaining unfertilised during ART and to identify the underlying mechanism of formation by means of polar body diagnosis (PBD) using the fluorescence-in-situ-hybridisation (FISH) technique.

Materials and methods: The study concerned 122 women (average age of 36.5±4.6 years) who underwent ART at the Fertility Center at Kaiser Wilhelm Memorial Church in Berlin from June, 2005 to February, 2006. Indications for PBD were previous unsuccessful ART cycles and/or advanced maternal age. First polar bodies of oocytes remaining unfertilised were analysed using FISH probes specific for chromosomes 13, 16, 18, 21 and 22.

Results: PBD provided analysable patterns of FISH signals in 263 out of 291 (90.4%) analysed polar bodies. Abnormal patterns of signals were indicated in 149 (56.6%) polar bodies; among them, gain or loss of single signals (=chromatids) were detected in 91 (61.1%) polar bodies and additional or missing double signals (=chromosomes) were detected in 17 (11.4%) polar bodies. 41 (27.5%) polar bodies showed aberrant signal patterns for more than one chromosome indicating multiple aneuploidies.

Conclusion: Oocytes showing fertilisation failure exhibit a surprisingly high aneuploid frequency of 56.6%, notwithstanding that only five chromosomes were tested. This supports the hypothesis that aneuploidy may be a cause for high rates of fertilisation failure during ART. Additionally, our results suggest that unbalanced premature division of chromatids is the main mechanism of aneuploidy formation in female gametes failing to fertilise.

The information of aneuploidy rate of unfertilised oocytes can serve as an important prognostic factor for patients having no or only poor fertilisation of their oocytes and who consider continuation of ART.