P-004 Impact of short abstinence versus testicular sperm on sperm DNA fragmentation: a systematic review and meta-analysis of prospective studies
Authors: Kugelman N , Hochberg A , Dahan M  H 
Published: July 2024

Abstract

Study question
Does testicular sperm result in lower sperm DNA fragmentation (SDF) compared to ejaculated sperm after short abstinence?

Summary answer
Testicular sperm exhibited significantly lower SDF than ejaculated sperm post-short abstinence.

What is known already
Optimal sperm DNA integrity is vital for fertilization and embryo health. Research shows testicular sperm typically exhibit lower SDF than ejaculated sperm with a standard abstinence period in the same individuals. Additionally, evidence indicates reducing abstinence to &lt; 2 days may decrease SDF, presenting a simpler, more cost-effective strategy than surgical retrieval. Yet, no studies have directly compared the efficacy of shorter abstinence against testicular sperm extraction for lowering SDF.

Study design, size, duration
Meta-analysis of 16 randomized controlled and prospective observational studies including four on testicular sperm (TESA or TESE, called TS) and twelve on short abstinence ejaculation. The meta-analysis followed MOOSE guidelines, scrutinizing databases including Cochrane Library, Web of Science, Embase, MEDLINE(R) and PUMBED up to November 16, 2023. The analysis was conducted using RevMan. The observational studies’ methodological quality was assessed using the Newcastle-Ottawa Scale, and the overall evidence quality was evaluated following the GRADE criteria.

Participants/materials, setting, methods
To compare short ejaculation duration and TESA (are not directly compared in the literature) for SDF levels, we analyzed relevant data from studies of each method. We adjusted the participant numbers in the TS group by 1/3 and included each TS study 3 times, to perform a comparison against the short duration studies which were in a ratio of 1:3. This approach maintained an unaltered cumulative subject count for the meta-analysis of TS studies.

Main results and the role of chance
A total of 641 patients were included, comprising 120 and 521 patients with SDF measurements following TS and ejaculation after a short abstinence period, respectively. The studies had varied inclusion criteria, with not all patients having an initial elevated SDF. Some studies had incomplete details on age and other demographics. However, the mean± SD age of 93 TS patients was 38.15± 5.48 years vs. 37.7± 6.0 years of 444 short abstinence patients, demonstrating no significant difference (P = 0.544). Short abstinence durations ranged from 1 to 48 hours. Diverse DNA fragmentation tests were used: TUNEL assay in three testicular sperm studies, SCD assay in one, and in the short abstinence group, 4 used TUNEL and 6 used SCD assays, along with one each using SCSA and Halosperm. The mean± SD SDF was lower in the TS group than in the short abstinence group (Mean difference -9.48, 95%CI -12.45 to -6.52, P &lt; 0.001, I2= 85%). Sensitivity analysis revealed that no single study significantly influenced the results. Employing the GRADE criteria, the initial assessment categorized the overall quality of evidence as low due to the observational nature of the acquired data. All studies were of medium to high quality.

Limitations, reasons for caution
Our meta-analysis, the first to compare two distinct methods for reducing SDF, while navigating through challenges of diverse study designs, variable patient characteristics, and differing DNA fragmentation tests. Despite these limitations, it marks a significant step in a field where direct, head-to-head comparisons have been absent, offering crucial insights.

Wider implications of the findings
This study suggests testicular sperm may be better than ejaculated sperm for improving SDF in infertility cases. Direct comparisons are needed, before deeming short abstinence less effective. Future research should directly compare reproductive outcomes using both methods.

Trial registration number
not applicable