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Superior Live Birth Rates, Reducing Sperm DNA Fragmentation (SDF), and Lowering Miscarriage Rates by Using Testicular Sperm Versus Ejaculates in Intracytoplasmic Sperm Injection (ICSI) Cycles from Couples with High SDF: A Systematic Review and Meta-Analysis
by
, , ,
Marina Cano-Extremera
†
,
Irene Hervas
†,
Alma Gisbert Iranzo
,
Mar Falquet Guillem
,
María Gil Juliá
,
Ana Navarro-Gomezlechon
,
Rosa Pacheco-Rendón
and
Nicolás Garrido Puchalt
* IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Avenida Fernando Abril Martorell, 106—Torre A, Planta 1ª, 46026 Valencia, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2025, 14(2), 130; https://doi.org/10.3390/biology14020130
Submission received: 9 December 2024
/
Revised: 10 January 2025
/
Accepted: 15 January 2025
/
Published: 26 January 2025
(This article belongs to the Section Biotechnology)
Simple Summary
The use of testicular sperm in non-azoospermic males has emerged in recent years as an attractive option for couples with high sperm DNA fragmentation (SDF) in the ejaculate, repeated ICSI failures, and even poor sperm quality. With this systematic review and meta-analysis, we aim to clarify the findings to date and provide updated information to guide clinical decisions. Our results indicate a clear decrease in the degree of SDF in testicular spermatozoa when compared to ejaculate, and their subsequent use in ICSI cycles leads to a significant increase in the clinical pregnancy rate and a decrease in the miscarriage rate, which is reflected in a significant increase in the rate of live birth at home. In addition, this clinical approach is much more effective in normozoospermic males with high SDF in the ejaculate and with at least one previously failed ICSI cycle. Nonetheless, the findings should be viewed with caution due to the low quality of the studies included and the limited evidence on the safety of this approach for offspring due to chromosome aneuploidies.
Abstract
This study aimed to compare sperm DNA fragmentation (SDF) levels between ejaculate and testicular sperm and evaluate clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles using testicular sperm (T-ICSI) versus ejaculate sperm (E-ICSI) in males with high ejaculate SDF, prior ICSI failures, or severe male infertility. A systematic review of major databases and a subsequent meta-analysis were performed to compare clinical outcomes in men with high SDF, oligozoospermia, or prior ICSI failures undergoing T-ICSI or E-ICSI. Thirteen studies met the inclusion criteria. Outcomes analyzed included SDF levels, fertilization rate (FR), clinical pregnancy rate (CPR), live birth rate (LBR) per embryo transfer (ET), and miscarriage rate (MR) per pregnancy. The mean difference (MD) and odds ratio (OR) were calculated for each outcome. Paired assessments of SDF showed significantly lower levels in testicular sperm compared to ejaculated sperm (MD = −25.42 [−31.47, −17.30], p < 0.00001). While no significant difference in FR was observed in T-ICSI cycles overall (OR = 0.94 [0.74, 1.20]), a subgroup analysis revealed significantly higher FR with E-ICSI in men with oligozoospermia and no prior ICSI failures (OR = 0.61 [0.52, 0.71], p < 0.00001). CPR was significantly higher in T-ICSI cycles (OR = 2.13 [1.35, 3.36], p < 0.001; n = 540 ET), along with a significantly lower MR (OR = 0.31 [0.14, 0.70], p = 0.004; n = 35) and increased LBR (OR = 2.40 [1.32, 4.36], p = 0.004; n = 446 ET). In conclusion, using testicular sperm in cases of elevated ejaculate SDF, oligozoospermia, or prior failed ICSI cycles enhances the selection of sperm with lower DNA damage, leading to improved pregnancy rates, reduced miscarriage rates, and higher live birth rates. However, the studies included were rated as having a moderate to serious risk of bias. Further well-designed randomized controlled trials are necessary to confirm these findings with stronger evidence.
