Introduction
Miscarriage is a devastating condition affecting a couple's current wellbeing and their relationship and life expectations. A sporadic miscarriage occurs in 15% of all clinical pregnancies, after detecting a fetal heartbeat. For women using home pregnancy testing kits and proving positive for a biochemical pregnancy, the incidence can reach 50% (Chard, 1991; Wilcox et al., 1998). Recurrent miscarriage is defined as ‘the loss of two or more pregnancies from the time of conception until 24 weeks of gestation’, as per the current European guideline, which has been reclassified from three consecutive pregnancy losses (Bender Atik et al., 2018). This is even more distressing to the couple and, despite a plethora of studies, few conclusive reasons exist for its occurrence (Aitken and De Iuliis, 2010); up to 30% remain unexplained and hence no robust treatments are available.
The spermatozoa and egg make equal contributions to the genome of the embryo; therefore, either could lead to fatal flaws at this stage of embryonic development, resulting in miscarriage. Yet, it is only recently that a link between sperm DNA and miscarriage has been explored. This has proved to be a useful route of enquiry as the integrity of sperm DNA is crucial for the accurate transmission of the father's genetic information to the embryo. Five systematic reviews and meta-analyses (Zini et al., 2008; Robinson et al., 2012; Osman et al., 2015; Zidi-Jrah et al., 2016; Tan et al., 2019) have reported that sperm DNA damage is significantly correlated to an increased risk of miscarriage after natural conceptions and after IVF and intracytoplasmic sperm injection (ICSI). At the time of publication of these reviews, few studies using the sensitive Comet assay had been undertaken (Kirkman-Brown and De Jonge, 2017).
The aims of the present study were to compare low, high and average damage levels between semen samples from fertile donors and men whose partners have had sporadic or recurrent miscarriage after natural conception and assisted reproductive technology (ART) conception to determine if the alkaline Comet assay can act as a biomarker for early pregnancy loss.