Criteria to evaluate patterns of segmental and complete aneuploidies in preimplantation genetic testing for aneuploidy results suggestive of an inherited balanced translocation or inversion.

OBJECTIVE: To define criteria for determining when preimplantation genetic testing for aneuploidy (PGT-A) results are suggestive of a potential balanced chromosomal rearrangement in the egg or sperm source and warrant karyotyping. DESIGN: Performance evaluation of criteria developed to assess PGT-A results for patterns of imbalances suggestive of a balanced chromosomal rearrangement in the egg or sperm source. SETTING: A single PGT-A laboratory and multiple in vitro fertilization centers. PATIENTS: Reproductive couples who underwent routine PGT-A testing. INTERVENTIONS: Karyotyping of reproductive couples for whom patterns of imbalances observed in PGT-A results suggested a balanced chromosomal rearrangement in the egg or sperm source. MAIN OUTCOME MEASURES: Correct or incorrect flagging of predicted translocation in either the egg or sperm source based on chromosome analysis. RESULTS: Proposed criteria correctly predicted a balanced reciprocal translocation in 97% of cases (n = 33), a (13;14) Robertsonian translocation in all cases (n = 3), and an inversion in all cases (n = 2). Other criteria evaluated were determined to be ineffective because of relatively low occurrences that met the criteria and/or low predictive value. CONCLUSIONS: Our results showed that the proposed criteria were effective for evaluating patterns of imbalances observed in PGT-A results suggestive of a potential chromosomal rearrangement in the egg or sperm source. Our proposed criteria can be employed by clinicians in the in vitro fertilization setting in combination with a patient's reproductive history to identify PGT-A patients who are likely carriers of balanced chromosomal rearrangements.

Aneuploidy Screening using Next Generation Sequencing.

Chromosomal aneuploidy is recognized to be a significant contributing factor in implantation failure and spontaneous miscarriage Hellani et al. (Reprod Biomed Online 17:841-847, 2008), Vanneste et al. (Nat Med 15:577-583, 2009) and is likely to be responsible for the majority of IVF failure [Baltaci et al. (Reprod Biomed Online 12:77-82, 2006), Munne (Placenta 24:S70-76, 2003)]. Preimplantation genetic testing for aneuploidy (PGT-A) screening, formerly termed preimplantation genetic screening (PGS), enables the assessment of the numeric chromosomal constitution in blastomere and/or trophectoderm biopsy before embryo transfer.Preimplantation genetic testing for aneuploidy (PGT-A) has been proven to improve the selection of embryos for transfer and therefore also assisted reproductive technology (ART) cycles. In this chapter we describe the current gold standard platform for PGT-A, next generation sequencing (NGS) protocol used in our laboratory.