Embryos whose polar bodies contain isolated reciprocal chromosome aneuploidy are almost always euploid

Abstract

STUDY QUESTIONWhen a chromosome aneuploidy is detected in the first polar body and a reciprocal loss or gain of the same chromosome is detected in the second polar body, is the resulting embryo usually aneuploid for that chromosome?SUMMARY ANSWERWhen reciprocal aneuploidy occurs in polar bodies, the resulting embryo is usually normal for that chromosome, indicating that premature separation of sister chromatids (PSSC)—not non-disjunction—likely occurred in meiosis I.WHAT IS KNOWN ALREADYSingle-nucleotide polymorphism-based microarray analysis can be used to accurately determine the chromosomal status of polar bodies and embryos. Sometimes, the only abnormality found is a reciprocal gain or loss of one or two chromosomes in the two polar bodies. Prediction of the status of the resulting embryo in these cases is problematic.STUDY DESIGN, SIZE, DURATIONBlinded microarray analysis of previously diagnosed aneuploid embryos that had reciprocal polar body aneuploidy.MATERIALS, SETTING, METHODSIVF cycles were performed between 2008 and 2011 in patients aged 40 ± 3 years (range 35–47 years) with an indication for polar body-based aneuploidy screening. Thirty-five aneuploid vitrified Day 3 embryos were warmed, cultured to Day 5 and biopsied for microarray analysis. Predictions were made for the ploidy status of the embryo if PSSC or non-disjunction had occurred. The signal intensity for the aneuploid chromosome in the first polar body was compared between those that resulted in euploid and aneuploid embryos.MAIN RESULTS AND THE ROLE OF CHANCEAmong 34 embryos with evaluable results, 31 were euploid on re-analysis. Of 43 chromosomes that had reciprocal aneuploidy in the polar bodies, 41 were disomic in the embryo, indicating that PSSC was likely to have occurred 95% (95% confidence interval 85–99%) of the time. The log 2 ratio signal intensity from the chromosomes that underwent non-disjunction, resulting in unbalanced embryos, were outliers when compared with those that underwent PSSC.LIMITATIONS, REASONS FOR CAUTIONAlthough most embryos with reciprocal aneuploid polar bodies were euploid, it is unknown whether they maintain equivalent reproductive potential when transferred. Further study is needed to determine whether these embryos should be re-biopsied and considered for transfer.WIDER IMPLICATIONS OF THE FINDINGSThis study is consistent with increasing evidence that PSSC is the primary cause of meiosis I errors in embryos from women of advanced reproductive age. Clinicians should be cautious in interpreting results from polar body aneuploidy screening, especially when only the first polar body is tested.STUDY FUNDING/COMPETING INTEREST(S)None.

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes

“…Conversely, nine our of 15 (60%) embryos derived from oocytes with aneuploid polar bodies resulted in a euploid trophectoderm biopsy. This finding is in keeping with previous studies, which have demonstrated that the primary mechanism responsible for aneuploidy in the first polar body is premature sister chromatid separation, allowing the possibility of reciprocal errors in meiosis II (Capalbo et al, 2013;Forman et al, 2013b;Gabriel et al, 2011;Treff et al, 2008). Therefore, it is expected that the accuracy of biopsy of the first polar body stage would not approach the efficiency of trophectoderm biopsy in improving implantation and ongoing pregnancy rates.…”

Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study

“…By using polar-body PGS, only maternally derived meiotic aneuploidies can be diagnosed, whereas mitotic aneuploidies, mosaicism and paternally derived aneuploidies, which are thought to contribute to 3-4% of chromosomal aberrations, are not detected by this method (Hassold and Hunt, 2001). Additionally, possible pitfalls of polar body analysis, such as trisomic rescue or reciprocal aneuploidy, resulting in euploid embryos after aneuploid tested polar bodies, have to be considered when comparing polar body and culture media genetic results (Forman et al, 2013). Up to 20% of embryos shown to be aneuploid by polar-body biopsy have been shown to be euploid after PGS analysis at the blastocyst stage, possibly caused by postzygotic rescue mechanisms (Capalbo et al, 2013;Christopikou et al, 2013;Handyside et al, 2012).…”

Reply: Questions about the accuracy of polar body analysis for preimplantation genetic screening

“…Even if no euploid embryos have been obtained at the blastocyst stage, there is no reason to assume that the limitation of PB screening observed here is unique to abnormal oocytes and embryos of poor prognosis AMA patients. Indeed, it has recently been demonstrated in a younger population that when reciprocal aneuploidy occurs from meiosis I premature separation of sister chromatids and compensation in meiosis II, the resulting embryo is usually normal for that chromosome (Forman et al, 2013) and also capable of producing a chromosomally normal child (Scott et al, 2012b). However, we agree that the reproductive potential of these embryos should be further evaluated.…”