This chapter describes the current clinical applications of noninvasive prenatal diagnosis (NIPD) for genetic conditions and the potential use for aneuploidy screening or diagnosis. It also highlights ethical, educational and laboratory aspects that require evaluation before introduction into routine clinical practice. The main clinical indications for fetal sex determination are risk of X-linked genetic disorder and family history of congenital adrenal hyperplasia (CAH), with occasional indications including some fetal ultrasound findings and discrepancy between genetic sex and the appearances of the external genitalia on fetal ultrasound. Regardless of the approach taken, results from relatively small numbers have been reported to date and therefore considerable effort is now needed, including formal validation, standardisation, education and other work, before NIPD for aneuploidy can be considered ready for implementation in routine clinical practice. NIPD based on cell-free fetal nucleic acids circulating in the maternal plasma will gradually move into clinical practice.

Laser-assisted polar body biopsy is best accomplished when the oocyte is affixed to the holding capillary with the first polar body at 12 O'clock position and the second polar body located right of the first one but in the same focal plane. In contrast to embryonic blastomeres, polar bodies are rather small and do not require any special pretreatment like hypo-osmotic swelling or pronase digestion. The size and position of openings drilled in the zona pellucida (ZP) can influence further embryonic development and in particular the mode of hatching at the blastocyst stage. The presence of a cytoplasmic bridge between the first as well as the second polar body and the oocyte can impose during biopsy. A frequent problem in analysis of the first polar body is high degree of fragmentation observed in human first polar bodies.

This chapter describes the data on pre-implantation genetic diagnosis (PGD) for aneuploidy screening (AS), focusing in two main topics: the chromosomal status of human gametes and embryos and the clinical application of PGD-AS in assisted reproductive technology (ART) and its controversies. In oocytes, the most frequent abnormalities detected were single chromosome trisomy and monosomy. The maternal origin of aneuploidy is prevalent in abnormal human conceptuses, and reproductive maternal aging is the important factor affecting the frequency of aneuploidy. Previous history of spontaneous abortions is a risk factor of pregnancy loss even in patients with normal karyotype. New evolving technologies will be able to significantly increase the sensitivity of PGD and reduce the diagnostic errors. Biological events such as mosaicism, postzygotes aneuploides, and trisomic rescue can cause diagnostic errors. With the view that efficiency can be significantly improved, PGD-AS has to be considered as a tool to implement ART procedure.