Sperm chromosome abnormalities in patients with normal karyotype and in translocation carriers: clinical relevance for assisted reproductive technology

Abstract

Research questionWhat is the proportion of chromosomally abnormal spermatozoa in men with a history of reproductive failure, including patients with normal karyotype and carriers of translocations? Should this analysis be included in a clinical setting to define the best treatment options for infertile couples? DesignAneuploidy for chromosomes XY, 13, 15, 16, 17, 18, 21, 22 was tested by fluorescent in-situ hybridization (FISH) in 1665 samples from couples with normal karyotype having had at least three previous IVF failures, miscarriages, or both (group-A). A FISH test was also carried out in 76 samples from carriers of translocations (group B) to detect the proportion of spermatozoa with unbalanced rearrangement. ResultsIn group A, the lowest incidence of aneuploid sperm cells was found in men with normozoospermia (1.3%, range 0.09–6.31%) compared with men with moderate oligoasthenoteratozoospermia (2.1%, range 0.41–16.6%, P < 0.001), severe oligoasthenoteratozoospermia (4.7%, range 0.53–30.77, P < 0.001), microepididymal sperm aspiration (3.1%, range 1.19–24.24, P < 0.001) and testicular sperm extraction samples (5.8%, range 1.54–33.3, P < 0.001). In group B, the proportion of spermatozoa with unbalanced rearrangement was significantly higher in reciprocal (63%, range 10.0–87.6%) than in Robertsonian translocations (16%, range 4.3–51.0%, P < 0.001). ConclusionsPatients with poor prognosis of term pregnancy tend to generate high proportions of chromosomally abnormal spermatozoa, especially in severe male factor cases. Corresponding frequencies occur at wide ranges; therefore, the FISH test is needed to assess the proportion of spermatozoa with altered chromosome condition. A flowchart, which included the FISH test, was designed to assist clinicians guide couples with poor prognosis of pregnancy, on the most indicated treatment options.