Clinical parameters associated with altered sperm DNA fragmentation index among primary infertile men: Findings from a real‐life cross‐sectional study

Abstract

BackgroundRecurrent pregnancy loss and unexplained infertility are the current indications to test sperm DNA fragmentation according to the European Association of Urology Guidelines on sexual and reproductive health.ObjectiveTo identify a novel and better performing model to diagnose primary infertile men presenting with altered sperm DNA fragmentation and to outline its predictive ability in respect to current European Association of Urology Guidelines’ recommendations.Materials and methodsData from the latest 515 consecutive primary infertile men as for World Health Organization criteria were analyzed. Semen analysis, sperm DNA fragmentation (according to sperm chromatin structure assay), and serum hormones were considered in every patient. Altered sperm DNA fragmentation was defined with levels greater than 30%. Descriptive statistics was applied to compare patients with normal versus SDF > 30%. The new predicting model was identified through logistic regression analysis exploring potential predictors of SDF > 30% at first clinical presentation. Diagnostic accuracy between the two predictive models (European Association of Urology Guidelines vs. new) was assessed, and decision curve analyses tested their clinical benefit.ResultsOf 515, 268 (51.9%) patients had SDF > 30% at clinical presentation. Patients with SDF > 30% were older (median [interquartile range] 39 [35–43] vs. 37 [34–41] years), had lower mean testicular volume (Prader 15 [12–20] vs. 17.5 [13.5–20] and lower total motile sperm count (1.80 [0.7–13.2] vs. 11.82 [4.2–44.5] × 106), all p < 0.001. No other clinical differences were depicted. The two groups showed similar rates of history of recurrent pregnancy loss and unexplained infertility. At multivariable logistic regression analysis, age more than 38 years (odds ratio: 2.43) and baseline total motile sperm count less than 20 × 106 (odds ratio: 3.72) were associated with SDF > 30%, after adjusting for Prader < 15, history of miscarriages and unexplained infertility, all p < 0.0001. The newly identified model (unexplained infertility + history of poli‐abortions + Prader < 15 + age ≥38 years + total motile sperm count <20 × 106) showed higher accuracy to identify SDF > 30% at baseline in respect to European Association of Urology Guidelines (area under the curve: 72.1 vs. 52.7), with superior clinical net benefit use.ConclusionsThe application of the European Association of Urology sexual and reproductive health guidelines does not ensure proper identification of primary infertile men with pathological sperm DNA fragmentation. We propose a novel and better performing predictive model to identify the infertile men with altered sperm DNA fragmentation at first clinical assessment.DiscussionAs altered sperm DNA fragmentation has been widely linked with the inability to conceive, this second‐level test could be further implemented over the diagnostic workup of a broader subset of patients presenting for male factor infertility. We propose a better performing model to identify this specific category of patients.

Sperm DNA integrity: a special issue exploring the causes, consequences, and treatment of DNA damage in human spermatozoa

“…However, we still have some way to travel. The development of novel consensus methods for detecting DNA damage, 14 determining which patients should be assessed, 30 elucidation of the relative importance of single and double strand breaks, 31 the significance of oxidative stress in the induction of such damage, 26 the potential therapeutic role for antioxidants, 32 and the consequences of sperm DNA damage in terms of male fertility and the health and wellbeing of the offspring, 23,24,26 all need to be elucidated before the true clinical significance of such damage becomes clear.…”

Productivity Index in Clinical Andrology: Research Directions on High-Impact Topics and in Particular on Male Infertility

“…Consequently, the extensive literature that has been published over the years led the World Health Organization in 2021 to introduce the SDF test as a test to be requested under certain circumstances for a better assessment of the fertility status, giving this test a diagnostic value and not only value in scientific research [30]. However, to date, there is still no consensus on which patients would benefit most from this diagnostic investigation and even scientific societies provide little guidance in this regard [31]. This is exactly why efforts are being made to identify which parameters can best predict which patients should be investigated for the presence of SDF.…”

Low-frequency neuromuscular electrical stimulation as a treatment for anejaculation caused by iatrogenic injury of the abdominal aorta: a case study

“…To determine the cause of the extremely low progressive sperm motility, it was suggested that the patient undergo testing for sperm DNA fragmentation if necessary. It was also considered that the long submission time of the semen sample could have affected sperm motility or that it could be a result of the operation itself [5].…”