ART strategies in Klinefelter syndrome



Patients with Klinefelter syndrome (KS) who receive assisted reproductive technology (ART) treatment often experience poor pregnancy rates due to decreased fertilization, cleavage, and implantation rates and even an increased miscarriage rate. Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients. In this review, we summarize the methods for guiding KS patients during ART and for developing optimal strategies for preserving fertility, improving pregnancy rate and live birth rate, and avoiding the birth of KS infants.


We searched PubMed and Google Scholar publications related to KS patients on topics of controlled ovarian stimulation protocols, sperm extraction, fertility preservation, gamete artificial activation, round spermatid injection (ROSI), and non-invasive prenatal screening (PGD) methods.


This review outlines the different ovulation-inducing treatments for female partners according to the individual sperm status in the KS patient. We further summarize the methods of retrieving sperm, storing, and freezing rare sperm. We reviewed different methods of gamete artificial activation and discussed the feasibility of ROSI for sterile KS patients who absolutely lack sperm. The activation of eggs in the process of intracytoplasmic sperm injection and non-invasive PGD are urgently needed to prevent the birth of KS infants.


The integrated strategies will pave the way for the establishment of ART treatment approaches and improve the clinical outcome for KS patients.

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The authors thank all members of the IVF center in Shanghai General hospital for helpful discussions when preparing this manuscript.


C.W, B. M, and Y. Y collected the information, analyzed the data, and wrote the manuscript. S. D, Y. Y, and S. J designed the pictures. Z. Z supervised the conception, design, and development of all aspects of the article and was involved in the data analysis and manuscript preparation. W. S, W. Y, F.Y, W.Y, and Z. Z review and editing of the final article. All the authors have seen and approved the final version.


This work was supported by grants from the National Natural Science Foundation of China (grants 81672562, 81872111, 81370074, 81902630), National Key Technology R&D Program of China (2019YFC1005200 and 2019YFC1005201), Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan (19XD1423100), the project of Outstanding Medical Doctor for ZZ, the cross project of Medical and Engineering (YG2016MS27), Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20181714), the projects sponsored by the development fund for Shanghai talents, the Shanghai Municipal Public Health Bureau (grant XYQ2013119), and the “Chenxing Project” from Shanghai Jiao Tong University to Z.Z.

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Chen, W., Bai, M.Z., Yang, Y. et al. ART strategies in Klinefelter syndrome. J Assist Reprod Genet (2020).

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  • Klinefelter syndrome
  • Administration strategy
  • Single sperm cryopreservation
  • TESE
  • Fertility preservation