Sperm recovery and ICSI outcomes in Klinefelter syndrome: A systematic review and meta-analysis

Giovanni Corona, Alessandro Pizzocaro, Fabio Lanfranco, Andrea Garolla, Fiore Pelliccione, Linda Vignozzi, Alberto Ferlin, Carlo Foresta, Emmanuele A. Jannini, Mario Maggi, Andrea Lenzi, Daniela Pasquali, Sandro Francavilla, Giancarlo Balercia, Marco Bonomi, Aldo Calogero, Andrea Fabbri, Felice Francavilla, Vito Giagullì, Rosario PivonelloAntonio Radicioni, Vincenzo Rochira, Giacomo Accardo, Biagio Cangiano, Rosita A. Condorelli, Giuliana Cordeschi, Settimio D'Andrea, Antonella Di Mambro, Daniela Esposito, Mariano Galdiero, Lara Giovannini, Antonio R.M. Granata, Sandro La Vignera, Giovanna Motta, Luciano Negri, Luca Persani, Ciro Salzano, Daniele Santi, Riccardo Selice, Manuela Simoni, Carla Tatone, Giacomo Tirabassi, Alberto Stefano Tresoldi, Enzo Vicari, On behalf of the Klinefelter ItaliaN Group (KING)

Research output: Contribution to journalArticle


BACKGROUND: Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified. OBJECTIVE AND RATIONALE: The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes. SEARCH METHODS: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional- TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included OUTCOMES: Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm. WIDER IMPLICATIONS: The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested.

Original languageEnglish
Article numberdmx008
Pages (from-to)265-275
Number of pages11
JournalHuman Reproduction Update
Issue number3
Publication statusPublished - May 1 2017


  • Assisted reproductive techniques
  • Fertility
  • Intra-cytoplasmic sperm injection
  • Klinefelter syndrome
  • Non-obstructive azoospermia
  • Testicular sperm extraction

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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    Corona, G., Pizzocaro, A., Lanfranco, F., Garolla, A., Pelliccione, F., Vignozzi, L., Ferlin, A., Foresta, C., Jannini, E. A., Maggi, M., Lenzi, A., Pasquali, D., Francavilla, S., Balercia, G., Bonomi, M., Calogero, A., Fabbri, A., Francavilla, F., Giagullì, V., ... On behalf of the Klinefelter ItaliaN Group (KING) (2017). Sperm recovery and ICSI outcomes in Klinefelter syndrome: A systematic review and meta-analysis. Human Reproduction Update, 23(3), 265-275. [dmx008]. https://doi.org/10.1093/humupd/dmx008