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

A pathogenic variant in the uncharacterized RNF212B gene results in severe aneuploidy male infertility and repeated IVF failure

“…demonstrated that poor prognosis of term pregnancy, especially in cases with severe male factor, is usually associated with high proportions of spermatozoa that display chromosome abnormality. 71 However, causative variants that may be responsible for these conditions have thus far not been associated with known PVs in meiosis-related genes, such as genes known to be involved in meiotic checkpoint and proper chromosomal pairing and segregation (e.g., SYCP3 , M1AP , TEX11 , MEIOB, and GCNA 15 , 72 , 73 , 74 , 75 ), since they all lead to meiotic arrest and complete absence of sperm cells in the ejaculate. 13 , 14 , 31 , 73 , 76 In contrast, the RNF212B C448T variant is, to the best of our knowledge, the first mutation in an essential human meiotic recombination gene that still allows the production of mature sperm cells with extensive aneuploidy.…”

Sperm Meiotic Segregation Analysis of Reciprocal Translocations Carriers: We Have Bigger FISH to Fry

“…The foremost point of this work was to examine whether spermFISH is a tool worthy to be used regularly for genetic counseling in RT carriers [ 3 , 9 ]. As some studies observed only a very weak trend between sperm balanced rates of RT carriers and embryos produced by PGD [ 3 , 9 ], only extreme values could be considered of interest. A patient with less than 10% of balanced gametes would suggest the production of a very low number of balanced embryos in PGD.…”

“…Balanced carriers of RTs are phenotypically normal as their genome contains the normal amount of chromosomal information despite being rearranged on different chromosomes. However, meiotic gametes production by RT carriers may lead to gametes with unbalanced chromosomal content and thus exposes them to higher risks of infertility, recurrent miscarriage, and fetus or children with congenital anomalies and developmental delay [ 2 , 3 ]. Therefore, the prevalence of RT increases to 0.6% in the infertile population, 1.2% in azoospermic men, 2.7% in couples with repeated implantation failures, and up to 6.9% in couples with recurrent miscarriages [ 4 , 5 , 6 ], establishing RTs as a major contributor to infertility.…”

“…The most important contribution of spermFISH would be its potential ability to be used as a predictor of the proportions of balanced embryos obtained after PGD fertilization. Unfortunately, recent studies on the subject find no correlations, or only a very weak trend, between balanced rates of sperm and embryos [ 3 , 9 ].…”

The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis

“…Unselected infertile men, as well as men with SDF, Robertsonian and reciprocal translocation, and those with a history of recurrent pregnancy loss are at increased risk of producing aneuploid sperm [33,34]. The manual addresses the utility of fluorescence in situ hybridization (FISH) as a diagnostic cytogenetic tool in the assessment of chromosomal aberrations and describes the FISH procedure, with emphasis on scoring criteria [35]. FISH is commonly used in the assessment of chromosomal aneuploidy involving chromosomes 13, 18, 21, X, and Y, which usually result in viable but defective births [36].…”