The use of fluorescent in situ hybridization in male infertility

Abstract

Male factors are implicated in up to 50% of couples being evaluated and treated for infertility with advanced assisted reproductive technologies. Genetic abnormalities, including sperm chromosome aneuploidy as well as structural aberrations, are one of the major causes of infertility. The use of chromosome-specific DNA probes labeled with fluorochromes, particularly the combination with multiple probes, has been used to indirectly study the sperm chromosome by fluorescent in situ hybridization (FISH). Clinically, this technique is also used to assess the sperm of men recovering from gonadotoxic treatment. Recent advances in this technology facilitate the evaluation of sperm aneuploidy. Sperm FISH is a widely used screening tool to aid in counseling couples with severe male factor infertility, especially in cases of prior repeated in vitro fertilization/intracytoplasmic sperm injection failure or recurrent pregnancy loss. Automation of FISH imaging and analysis, as well as the development of emerging techniques such as comparative genomic hybridization, will all contribute to the promise of future diagnostic approaches aimed at improving the quality, ease, and efficiency of aneuploidy analysis.

Keywords: chromosome abnormalities; clinical relevance; male infertility; sperm fluorescent in situ hybridization.

Figure 1.

Fluorescent in situ hybridization (FISH) analysis of all 46 chromosomes in an XX phenotypic male. The patient stained positive (red) for the SRY region at the tail of one of the X chromosomes.

Figure 2.

Examples of sperm fluorescent in situ hybridization (FISH). Top left: normal X- and Y-bearing sperm. Top right: sperm with chromosome 18 and XY disomy. Bottom left: sperm with sex chromosome XY disomy. Bottom right: sperm with chromosome 13 and 18 disomy.