Prospective reproductive outcomes according to sperm parameters, including DNA fragmentation, in recurrent pregnancy loss

Research question: Are the prospective reproductive outcomes in couples experiencing recurrent pregnancy loss (RPL) related to the sperm DNA fragmentation index (DFI), as measured by sperm chromatin structure assay, sperm morphology and sperm concentration at referral?

Design: This prospective cohort study included 95 couples seen between 1 April 2018 and 1 December 2019 at the tertiary Copenhagen RPL Unit, Copenhagen University Hospital, Rigshospitalet and Hvidovre Hospital, Denmark. The couples had experienced three or more unexplained consecutive pregnancy losses or two late pregnancy losses (>12 weeks gestation). Follow-up was 12-31 months.

Results: Eighty-one of 95 (85.3%) couples achieved pregnancy after referral. In the first pregnancy after referral, 46 (56.8%) couples achieved a live birth, and 35 (43.2%) couples experienced another pregnancy loss. There was no significant difference in baseline DFI between couples that experienced pregnancy loss [median 11.7, interquartile range (IQR) 9.1-17.3] and couples that achieved a live birth (median 12.5, IQR 9.3-16.5; P = 0.971). Improving sperm morphology increased the odds of a live birth after referral (adjusted OR 1.26, 95% CI 1.05-1.52; P = 0.014). DFI and sperm concentration were not associated with the outcome of the first pregnancy after referral. Overall, 35.9% of the men had DFI ≥15 at inclusion. Couples that failed to achieve pregnancy had a higher median DFI of 17.7 (IQR 7.7-27.2) compared with the rest of the cohort (median 12.0, IQR 9.3-16.5; P = 0.041).

Conclusions: At referral, sperm DFI, morphology and concentration cannot be used to identify RPL couples at risk of another pregnancy loss. Increased baseline DFI was associated with difficulty achieving another pregnancy, and improving sperm morphology was associated with increased odds of a live birth.