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Hum Reprod Update. 2017 May 1;23(3):265-275. doi: 10.1093/humupd/dmx008.

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

Author information

Endocrinology Unit, Medical Department, Endocrinology Unit, Azienda Usl Bologna Maggiore-Bellaria Hospital, Via Altura 3, 40139 Bologna, Italy.
Endocrinology Unit, IRCCS, Humanitas Research Hospital, Rozzano, Via Manzoni 56, 20089 Milan, Italy.
Department of Medical Sciences, Division of Endocrinology, Diabetology and Metabolism, University of Torino, Corso Dogliotti 14, 10126 Turin, Italy.
Department of Medicine, Andrology and Reproductive Medicine Unit, University of Padova, Via Giustiniani 2, 35100 Padova, Italy.
Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, Sexual Medicine and Andrology Unit, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
Department of Systems Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00166 Rome, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Via Pansini 5, 80131 Naples, Italy.
Department of Life, Health and Environmental Sciences, University of L'Aquila, Via Vetoio, 67100 L'Aquila, Italy.



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.


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.


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.


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.


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.


Klinefelter syndrome; assisted reproductive techniques; fertility; intra-cytoplasmic sperm injection; non-obstructive azoospermia; testicular sperm extraction

[Indexed for MEDLINE]

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