P-549 Paraclinical and spermogram evaluation of infertile males with balanced chromosomal rearrangements referred to Royan institute from 2009-2021

Abstract

Abstract Study question Whether balanced chromosomal rearrangements are associated with altered semen parameters/increased DNA Fragmentation Index (DFI), are the common breakpoints related to male infertility in patients ? Summary answer Balanced chromosomal rearrangements is associated with abnormal semen parameters and increased DFI in carriers. Chromosomes 9,1,3 showed the highest incidence of chromosomal rearrangement What is known already Among many factors, balanced chromosomal rearrangements are thought to be one of the major genetic factors influencing male infertility which can cause disorders related to spermogram, DNA fragmentation, increased risk of miscarriage and ART failure. Finding common chromosomal breakpoints in infertile men carrying balanced chromosomal translocations is significant since these patients usually possess normal clinical features. Numerous studies have been performed on the various chromosome translocations. However, there has not been any report on the common breakpoints in balanced chromosomal abnormalities related to male infertility in Iran. Study design, size, duration This cross-sectional study performed on 25000 patients’ files admitted to the Royan institute during the period 2009- 2021.Infertile men carrying balanced chromosomal rearrangements were included as case group. Sperm parameters, DFI and common chromosomal break points were evaluated Participants/materials, setting, methods 25000 files of patients were reviewed. 252 infertile men carrying balanced chromosomal rearrangements and 252 men with normal karyotype were included (case and control group, respectively). Sperm concentration, motility (CASA), sperm morphology (Papanicolaou Staining),DFI (SCSA) and cytogenetic analysis of peripheral blood lymphocytes (G-banding) were evaluated. Numerical chromosomal abnormalities, deletions, marker chromosomes, alcohol or drug addiction, smoking, chemotherapy and radiation, varicocele and exposure to environmental pollution were excluded. The common chromosomal breakpoints in translocations were investigated. Main results and the role of chance Sperm concentration, total motility and normal morphology were significantly lower in balanced chromosomal rearrangements carriers compared to control group(p < 0.05). DFI in patient was significantly higher in comparison to control group(p < 0.05). Among different kind of chromosomal rearrangement carriers’, sperm concentration and total motility were lower in Robertsonian translocation carriers comparing to the Reciprocal translocation and inversion ones. The reciprocal translocation and inversion carriers did not differ regarding to sperm concentration and total motility. Meanwhile, normal morphology was lower in the translocation compared to inversion carriers. No difference was observed in DFI among carriers of balanced chromosomal rearrangements. Among case group, inversion accounted for the largest share, followed by Reciprocal, Robertsonian translocation and insertion. Group C had the highest frequency in reciprocal translocation, inversion and insertion among the chromosomal groups. The highest balanced translocation prevalence was related to three chromosomes 9,3, and1. 9q12,1p36,3p11 were the most frequent breakpoints among them. Chromosome 9 had the largest contribution to inversions,22 to reciprocal translocations and14 to Robertsonian translocations. In the Robertsonian translocation, group D showed the highest frequency. Interestingly, patients carrying normal variations such as pericentric inversion of chromosome 9showed a significant alteration in sperm parameters, therefore normal variations showed a possible relationship to infertility. Limitations, reasons for caution In order to achieve stronger statistical results on DFI, a larger sample size would be more helpful. Wider implications of the findings The results may be useful to identify the most common breakpoints and consequently genes related to male infertility and can suggest appropriate molecular mechanism for their infertility. Trial registration number not applicable