Intracytoplasmic sperm injection (ICSI) has been widely used to overcome all forms of male factor infertility. Despite its overall acceptable success rates with the use of abnormal sperm, studies suggest that low sperm quality may adversely impact ICSI outcomes, likely due to altered sperm DNA content associated with impaired sperm characteristics.1-3 The negative impact of damaged paternal chromatin is usually manifested by impaired embryo development and early pregnancy loss, thus decreasing assisted reproductive therapy success.4
Sperm DNA fragmentation (SDF) assays measure the proportion of sperm with damaged chromatin in the neat ejaculate.4 Among couples undergoing ICSI, high SDF in the neat semen is found in ~30% of men.5 In recent studies, we found that the use of testicular sperm in preference over ejaculated sperm may offer better ICSI outcomes for men with high SDF in semen.6 The biological plausibility seems to be related to increased SDF in ejaculated, compared to testicular sperm, most probably due to elevated levels of reactive oxygen species in the epididymis that can cause post-testicular harm.7
At the European Society of Human Reproduction and Embryology (ESHRE) congress 2017, hosted in Geneva, Switzerland, these findings were presented concerning a PRISMA systematic review and meta-analysis of ICSI outcomes for testicular (Testi-ICSI) and ejaculated (Ejac-ICSI) sperm among non-azoospermic infertile men with confirmed post-testicular SDF. Our electronic search into major databases up to December 2016 identified seven studies, encompassing 507 ICSI cycles and 3,840 injected oocytes. Five studies provided paired data on SDF between ejaculated and testicular sperm, involving 143 patients who served as their own control. High SDF was defined according to the method and thresholds used in each study, most often terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and 30%, respectively.
We found that SDF rates were lower in testicular rather than ejaculated sperm, with the mean difference by random-effect model (REM) being -24.58% (95% confidence interval [CI]: -32.53, -16.64; I2=92%; p<0.001). The pooled odds ratio (OR) for fertilisation rates using REM was 0.81 (95% CI: 0.58–1.15; I2=81%; p=0.24), with a trend to lower fertilisation rates in the Testi-ICSI group. Clinical pregnancy rates per fresh embryo transfer were higher with Testi-ICSI than Ejac-ICSI, with an OR using the fixed effects model (FEM) of 2.42 (95% CI: 1.57–3.73; I2=34%; p<0.001). As for miscarriage rates, we found that results favoured Testi-ICSI as compared to Ejac-ICSI, with an OR by FEM of 0.28 (95% CI: 0.11–0.68; p=0.005; I2=11%). Lastly, live birth rates per fresh embryo transfer were higher with Testi-ICSI as compared with Ejac-ICSI, with an OR by FEM of 2.58 (95% CI: 1.54–4.35; I2=0%; p<0.001).
To our knowledge, this is the first systematic review and meta-analysis summarising the evidence currently available concerning Testi-ICSI in men with high SDF in neat semen. Our findings offer novel insights on SDF-related infertility and offer a possible therapeutic approach with the use of Testi-ICSI. Given the overall moderate quality of studies included in our meta-analysis, and the risks associated with sperm retrieval, the use of testicular over ejaculated sperm should be considered only in ICSI candidates with confirmed post-testicular SDF. In particular, couples with previous failed treatment cycles, where efforts to reduce SDF in the ejaculate have also failed, then injected sperm should be used.