Article Data

  • Views 209
  • Dowloads 111

Systematic review

Open Access

Reproductive outcomes of testicular and ejaculated sperm for ICSI in patients with previous ICSI failures: a systematic review and meta-analysis

  • Xiao-Wei Yu1
  • Yan-Hong Liu1
  • Xiao-Yuan Zhang1
  • Qun Wang1

1Center for Reproductive Medicine and Center for Prenatal Diagnosis, Jilin University First Hospital, 71 Xinmin Street, Chaoyang District, 130021 Changchun, Jilin Province, China

DOI: 10.31083/jomh.2021.044

Submitted: 17 January 2021 Accepted: 05 March 2021

Online publish date: 09 June 2021

*Corresponding Author(s): Qun Wang E-mail:

PDF (2 MB) Supplementary material


This systematic review aims to compare and evaluate the outcome of using either testicular sperm (Testi-ICSI) or ejaculated sperm (Ejac-ICSI) in intracytoplasmic sperm injections in patients with recurrent ICSI failure. The Cochrane Library, MEDLINE, EMBASE, and PubMed were used to search for relevant papers up till October 2020. Four cohort studies and two case series studies were included. Four studies investigated males with high sperm DNA fragmentation (SDF) and were classified as ''high SDF'', which included 247 couples and 2712 injected oocytes. The other three studies provided paired data to an unselected population of infertile men with either untested SDF or when anomalous SDF was not used as the basis for deciding to use Testi-ICSI, and were classified as ''noclassify'' in this study. This subgroup consisted of a total of 290 couples and 1061 injected oocytes. There was a higher level of clinical pregnancy rates (CPRs) in the ''high SDF'' subgroup when Testi-ICSI was used as compared to Ejac-ICSI, at 43.4% and 20.8% respectively, with a pooled odds ratio (OR) of 2.87 (95% confidence interval (CI) 1.44–5.71; P = 0.003). Furthermore, in the ''high SDF'' subgroup, Testi-ICSI use was associated with better take home baby rates (38%) as compared to Ejac-ICSI (16%), with a pooled OR of 3.24 (95% CI 1.20–8.76; P = 0.02). In the ''noclassify'' group, there was no statistically significant difference in the CPRs and take home baby rates of Testi-ICSI and Ejac-ICSI, although there was a trend of better CPRs and take home baby rates with Testi-ICSI use. Utilization of Testi-ICSI in recurrent ICSI failure couples, where males were confirmed to have high SDF in their ejaculated sperm, were correlated with greater CPRs and take home baby rates. However, Testi-ICSI may not result in better ICSI outcomes among men with untested SDF or when anomalous SDF was not the main factor influencing the decision to utilize Testi-ICSI.


Intracytoplasmic sperm injection; Male infertility; Sperm retrieval; Testicular spermatozoa; Sperm DNA fragmentation

Cite and Share

Xiao-Wei Yu,Yan-Hong Liu,Xiao-Yuan Zhang,Qun Wang. Reproductive outcomes of testicular and ejaculated sperm for ICSI in patients with previous ICSI failures: a systematic review and meta-analysis. Journal of Men's Health. 2021.doi:10.31083/jomh.2021.044.


[1] Mekinian A, Cohen J, Alijotas-Reig J, Carbillon L, Nicaise-Roland P, Kayem G, et al. Unexplained recurrent miscarriage and recurrent implantation failure: is there a place for immunomodulation?American Journal of Reproductive Immunology. 2016; 76: 8–28.

[2] Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertility and Sterility. 2010; 93: 1027–1036.

[3] Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline. Fertility and Sterility. 2013; 99: 673–677.

[4] Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Human Reproduction. 2007; 22: 174–179.

[5] Santi D, Spaggiari G, Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management—meta-analyses. Reproductive BioMedicine Online. 2018; 37: 315–326.

[6] Halpern JA, Brannigan RE, Schlegel PN. Fertility-enhancing male reproductive surgery: glimpses into the past and thoughts for the future. Fertility and Sterility. 2019; 112: 426–437.

[7] Esteves SC, Roque M, Bradley CK, Garrido N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertility and Sterility. 2017; 108: 456–467.e1.

[8] Ambar RF, Agarwal A, Majzoub A, Vij S, Tadros NN, Cho CL, et al. The use of testicular sperm for intracytoplasmic sperm injection in patients with high sperm DNA damage: a systematic review. The World Journal of Men’s Health. 2020. (in press)

[9] Young D. Surgical treatment of male infertility. Journal of Reproduc-tion and Fertility. 1971; 23: 541–542.

[10] Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. British Medical Journal. 2016; 355: i4919.

[11] Chen B, Benedetti A. Quantifying heterogeneity in individual partic-ipant data meta-analysis with binary outcomes. Systematic Reviews. 2017; 6: 243.

[12] Gilman AR, Younes G, Tannus S, Son WY, Chan P, Buckett W. Does using testicular sperm retrieval rather than ejaculated spermatozoa improve reproductive outcomes in couples with previous ART failure and poor ovarian response? A case-controlled study. Andrology. 2018; 6: 142–145.

[13] Zini A, Alharbi M, Hamouche F, Phillips S, Kadoch JI. Use of testicular sperm in couples with SCSA-defined high sperm DNA fragmentation and failed intracytoplasmic sperm injection using ejaculated sperm. Asian Journal of Andrology. 2020; 22: 348–353.

[14] Herrero M, Lusignan M, Son WY, Sabbah M, Buckett W, Chan P. ICSI outcomes using testicular spermatozoa in non‐azoospermic couples with recurrent ICSI failure and no previous live births. Andrology. 2019; 7: 281–287.

[15] Pabuccu EG, Caglar GS, Tangal S, Haliloglu AH, Pabuccu R. Testicular versus ejaculated spermatozoa in ICSI cycles of normozoospermic men with high sperm DNA fragmentation and previous ART failures. Andrologia. 2017; 49: e12609.

[16] Arafa M, AlMalki A, AlBadr M, Burjaq H, Majzoub A, AlSaid S, et al. ICSI outcome in patients with high DNA fragmentation: Testicular versus ejaculated spermatozoa. Andrologia. 2018; 50: e12835.

[17] Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Human Reproduction. 2005; 20: 226–230.

[18] Awaga HA, Bosdou JK, Goulis DG, Chatzimeletiou K, Salem M, Roshdy S, et al. Testicular versus ejaculated spermatozoa for ICSI in patients without azoospermia: a systematic review. Reproductive Biomedicine Online. 2018; 37: 573–580.

[19] Abhyankar N, Kathrins M, Niederberger C. Use of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with cryptozoospermia: a meta-analysis. Fertility and Sterility. 2017; 105: 1469–1475.e1.

[20] Kang Y, Hsiao Y, Chen C, Wu C. Testicular sperm is superior to ejaculated sperm for ICSI in cryptozoospermia: an update systematic review and meta-analysis. Scientific Reports. 2018; 8: 1–9.

[21] Ku FY, Wu CC, Hsiao YW, Kang YN. Association of sperm source with miscarriage and take-home baby after ICSI in cryptozoospermia: a meta-analysis of testicular and ejaculated sperm. Andrology. 2018; 6: 882–889.

[22] Strassburger D, Friedler S, Raziel A, Schachter M, Kasterstein E, Ron-el R. Very low sperm count affects the result of intracytoplasmic sperm injection. Journal of Assisted Reproduction and Genetics. 2000; 17: 431–436.

[23] Mitchell V, Rives N, Albert M, Peers M, Selva J, Clavier B, et al. Outcome of ICSI with ejaculated spermatozoa in a series of men with distinct ultrastructural flagellar abnormalities. Human Reproduction. 2006; 21: 2065–2074.

[24] Mehta A, Esteves SC, Schlegel PN, Niederberger CI, Sigman M, Zini A, et al. Use of testicular sperm in nonazoospermic males. Fertility and Sterility. 2018; 109: 981–987.

[25] Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertility and Sterility. 1997; 68: 519–524.

[26] Zini A, Bielecki R, Phang D, Zenzes MT. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertility and Sterility. 2001; 75: 674–677.

[27] Luke B, Brown MB, Wantman E, Lederman A, Gibbons W, Schattman GL, et al. Cumulative birth rates with linked assisted reproductive technology cycles. New England Journal of Medicine. 2012; 366: 2483–2491.

[28] Moskovtsev SI, Alladin N, Lo KC, Jarvi K, Mullen JBM, Librach CL. A comparison of ejaculated and testicular spermatozoa aneuploidy rates in patients with high sperm DNA damage. Systems Biology in Reproductive Medicine. 2012; 58: 142–148.

[29] Cheung S, Schlegel PN, Rosenwaks Z, Palermo GD. Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype. PLoS ONE. 2019; 14: e0210079.

[30] Qiu Y, Yang H, Li C, Xu C. Progress in research on sperm DNA fragmentation. Medical Science Monitor. 2020; 26: e918746–918741.

[31] Ribas-Maynou J, García-Peiró A, Fernández-Encinas A, Abad C, Amengual MJ, Prada E, et al. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology. 2013; 1: 715–722.

Abstracted / indexed in

Science Citation Index Expanded Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Social Sciences Citation Index Social Sciences Citation Index contains over 3,400 journals across 58 social sciences disciplines, as well as selected items from 3,500 of the world’s leading scientific and technical journals. More than 9.37 million records and 122 million cited references date back from 1900 to present.

Current Contents - Social & Behavioral Sciences Current Contents - Social & Behavioral Sciences provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in the social and behavioral sciences.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

SCOPUS Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

DOAJ DOAJ is a community-curated online directory that indexes and provides access to high quality, open access, peer-reviewed journals.

CrossRef Crossref makes research outputs easy to find, cite, link, assess, and reuse. Crossref committed to open scholarly infrastructure and collaboration, this is now announcing a very deliberate path.

Portico Portico is a community-supported preservation archive that safeguards access to e-journals, e-books, and digital collections. Our unique, trusted process ensures that the content we preserve will remain accessible and usable for researchers, scholars, and students in the future.

Submission Turnaround Time