Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: results from a multicenter case-control study

Background: Sperm DNA fragmentation (SDF) was hypothesized to have a role in the pathogenesis of recurrent pregnancy loss (RPL). Unfortunately, the quality of already published evidence is low. Objectives: To investigate the association between SDF and idiopathic RPL by limiting as much as possible the interference of confounding factors MATERIALS AND METHODS: This was a retrospective multicenter case-control study conducted in two Italian University Hospitals (i.e., Policlinico Gemelli, Rome and Humanitas S. Pio X, Milan) from July 2020 to March 2022. Cases were men belonging to couples affected by first trimester idiopathic RPL defined as the previous loss of two or more pregnancies. Two control groups were selected: i) men belonging to couples with proven fertility (i.e., at least two previous full-term pregnancies) (control group A); ii) men belonging to couples with proven infertility (i.e., the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse) (control group B). The SDF index (sDFI) was measured by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Results: We included 74 cases, 37 men with proven fertility (control group A) and 100 men belonging to infertile couples (control group B). The median sDFI was significantly lower in control group A (17%, interquartile range (IQR): 14.3-20.6%) compared to both case group (24.5%, IQR: 17-32%; p < 0.0001) and control group B (24%, IQR: 18.9-30%; p = 0.001). The rate of subjects with sDFI >30% was significantly higher in both case group (28%, 95% confidence interval (CI) [18, 40%]) and control group B (26%, 95%CI [18, 36%]) compared to control group A (0%, 95% CI [0, 10%]) (p < 0.001). Multivariate regression models yielded a significant association between sDFI and RPL (adjusted odds ratio (aOR) 1.13, 95%CI [1.04, 1.23], p = 0.006) but failed to show an association between sDFI and infertility (aOR 1.13, 95%CI [1, 1.29], p = 0.05). Conclusions: Men within couples affected by RPL or infertility had a significantly higher rate of SDF compared to fertile controls. However, after adjusting for covariates, sDFI was associated only with RPL. This article is protected by copyright. All rights reserved.