Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception

Abstract

Purpose Standard semen parameters are poor predictors of fertility potential. To date, apart from, paternal karyotyping sperm factors are not evaluated in recurrent pregnancy loss (RPL), only recent studies have emphasized the role of sperm factors in early embryonic development as sperm transcribes genes critical for early embryonic development. Sperm DNA integrity is useful diagnostic and prognostic marker and has clinical implications in idiopathic recurrent pregnancy loss (iRPL) following spontaneous conception. The aim of this study was to assess DNA integrity in cases experiencing iRPL following spontaneous conception. Methods Semen samples from 45 patients and 20 controls were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was used to measure DNA fragmentation index (DFI). Results By applying receiver operating curve (ROC) analysis, sperm DFI of approximately 26 % was found in male partner of couples experiencing iRPL. Conclusions Our data indicate that sperm from men with a history of iRPL have a higher percentage of DNA damage as compared to control group, and this can explain pregnancy loss in these patients. Men with higher DFI are infertile whereas men with lower DFI (26 %) are able to conceive but experience recurrent pregnancy loss. Thus it is important to evaluate sperm DFI in couples experiencing iRPL to understand exact aetiology of RPL and determine prognosis and management.

Histone retention, protein carbonylation, and lipid peroxidation in spermatozoa: Possible role in recurrent pregnancy loss

“…The deleterious effect of fragmented paternal DNA on embryonic viability and progression of pregnancy has been experimentally shown in mouse models [Ahmadi and Ng 1999] and similar results were also observed in human patients who opt for assisted reproductive technologies such as IVF and ICSI [Lin et al 2008;Muriel et al 2006;Robinson et al 2012;Tandara et al 2014;Tesarik et al 2004;Wdowiak et al 2015;Zhao et al 2014;Zini et al 2008]. In idiopathic cases of recurrent miscarriages too, the higher rates of sperm DNA fragmentation have been implicated, in the absence of any detectable female factor abnormality [Absalan et al 2012;Brahem et al 2011;Carrell et al 2003;Kumar et al 2012;Ramasamy et al 2015;Ribas-Maynou et al 2012;Zidi-Jrah et al 2016]. In congruence, studies have also reported interrelations between sperm chromatin alterations and early embryo post-implantation development in couples undergoing ART [ (Borini et al 2006;Seli et al 2004].…”

Impact of obesity on male fertility, sperm function and molecular composition

“…Sperm DNA integrity is important for successful fertilization and normal embryonic development, as evidenced by sperm with poor DNA integrity being negatively correlated with successful pregnancies 36 - 40 . Furthermore, sperm oxidative stress correlated with decreased sperm motility, increased sperm DNA damage, decreased acrosome reaction and lower embryo implantation rates following IVF 41 - 43 .…”

Novel insights into the genetic and epigenetic paternal contribution to the human embryo

“…The chromatin in mammalian sperm can broadly be divided into three major structural domains: (1) the vast majority of sperm DNA is coiled into toroids by protamines, (2) a much smaller percent (5-15%) remains bound to histones and thus retains its nucleosomal structure, and (3) DNA that is attached to the sperm nuclear matrix at MARs (matrix attachment regions) at intermediate intervals of approximately 50 kb throughout the genome (9). Sperm chromatin is essential for sperm function and subsequent embryonic development; defects in sperm chromatin have been linked to natural reproductive malfunctions, such as spontaneous abortion and assisted reproductive failure (10-12). These defects can include disrupted DNA integrity, which may affect fecundity and embryo growth, leading to embryo loss (13-15).…”