Are Tests of Sperm DNA Damage Clinically Useful? Pros and Cons

Abstract

The advent of assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI), has revolutionized the treatment of male-factor infertility. However, there are many unanswered questions regarding the safety of these techniques. These safety concerns are relevant because 1) these technologies often bypass the barriers to natural selection; 2) infertile men, particularly those with severe male-factor infertility, possess substantially more sperm DNA damage than do fertile men; and 3) experimentally, sperm DNA damage has been shown to adversely affect the developing embryo. This review discusses the etiology of sperm DNA damage, describes the individual tests of sperm DNA damage, and explores the relationship between sperm DNA damage and pregnancy outcomes. Based on a systematic review of the literature, sperm DNA damage is associated with lower natural, intrauterine insemination (IUI), and in vitro fertilization (IVF) pregnancy rates, but not with ICSI pregnancy rates. The literature also suggests that that sperm DNA damage is associated with an increased risk of pregnancy loss in those couples undergoing IVF or ICSI. Nonetheless, the true clinical utility of sperm DNA damage tests remains to be established, because the available studies are small and few in number and the study characteristics are heterogeneous. Although current data suggest that impaired sperm DNA integrity may have the greatest effect on IUI pregnancy rates and pregnancy loss by IVF and ICSI, further prospective studies are needed before testing should become a routine part of patient management.

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

“…The ASRM Practice Committee [52] does not recommend the routine application of sperm DNA tests, but studies have shown that sperm DNA damage is predictive of a low potential for natural fertility and a prolonged time to pregnancy [22,48,53]. Furthermore, sperm DNA damage may adversely impact intra-uterine insemination outcomes and to a lesser degree IVF pregnancy rates, but not IVF/ICSI pregnancy rates [3,10,22,48,[52][53][54][55]. Sperm DNA damage is also associated with a significantly increased risk of pregnancy loss after IVF and ICSI [56,57].…”

“…genetic or developmental abnormalities) or due to secondary or extrinsic factors causing testicular or posttesticular injury (e.g. gonadotoxins, hyperthermia, oxidants, endocrine abnormalities) [2][3][4][5][6][7][8][9][10]. Investigators have suggested that protamine deficiency (with aberrant chromatin remodeling), reactive oxygen species (ROS) and abortive apoptosis may cause sperm DNA damage [11][12][13][14][15][16][17][18].…”

Blastocyst transfer and gender: IVF versus ICSI

“…Sperm DNA damage is associated with significantly lower IVF pregnancy rate [33,34]. In an early study of Ray et al on fresh surplus embryos after in vitro fertilization [25], 63 % of the blastocysts examined, were female.…”

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

“…A systematic review of the literature demonstrates that sperm DNA damage is associated with lower pregnancy rates after assisted conception techniques, namely, intrauterine insemination and in-vitro fertilization (IVF) and to a lesser extent with intracytoplasmic sperm injection (ICSI) [8,9,36]. Nonetheless, sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and after ICSI, and because ICSI bypasses the natural defense barriers and allows for fertilization with DNA damaged sperm, there is growing concern regarding the health of the resulting offspring [14,41].…”