Int J Med Sci 2020; 17(9):1136-1141. doi:10.7150/ijms.46058

Research Paper

Possible misdiagnosis of 46,XX testicular disorders of sex development in infertile males

Tong Chen1,2†, Linlin Tian1,3†, Xianlong Wang1, Demin Fan4, Gang Ma1, Rong Tang1, Xujun Xuan1,5 ✉

1. Center for Reproductive Medicine, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, Shandong 250021, P.R. China
2. Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, P.R. China
3. Department of microbiology, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
4. Department of Urology, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250002, P.R. China
5. Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, P.R. China.
Tong Chen and Linlin Tian contributed equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Chen T, Tian L, Wang X, Fan D, Ma G, Tang R, Xuan X. Possible misdiagnosis of 46,XX testicular disorders of sex development in infertile males. Int J Med Sci 2020; 17(9):1136-1141. doi:10.7150/ijms.46058. Available from

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Objectives: The 46,XX disorders of sex development (DSD) is a rare genetic cause of male infertility and possible misdiagnosis of this condition has never been reported. We aim to investigate clinical characteristics and laboratory results of infertile males with possibly misdiagnosed 46,XX DSD.

Methods: Between January 2008 and December 2017, a retrospective case series study was performed involving sixteen 46,XX DSD males without azoospermia factor (AZF) deletion. Demographics, clinical features, laboratory results and assisted reproductive technology (ART) outcomes of these patients were depicted, and the underlying accurate diagnosis was also discussed.

Results: The mean age was 30.06 ± 5.40 years old. Thirteen patients (81.25%) merely obtained secondary school education. Gynaecomastia occurred in one case, and cryptorchidism appeared in two cases. Testicular volumes were equal to 15 mL on two sides in one patient who had severe asthenozoospermia. Thirteen patients (81.25%) had bilateral atrophic testes which were below 5 mL. The majority of patients were observed with elevated levels of gonadotropic hormones and decreased testosterone values. Neither AZF region nor sex-determining region Y gene was absent among all patients. Twelve patients had normal ejaculatory function, whereas four were diagnosed with ejaculatory dysfunction. Eleven patients (68.75%) were diagnosed with azoospermia. Testicular sperm aspiration was performed in six subjects (37.50%). The pathological results showed that Leydig cell hyperplasia with spermatic failure was found in each case, and no sperm was found in testicular tissue. ART with donor sperm was conducted in 15 patients. Live birth was achieved in three cases through artificial insemination by donor and in one case using in-vitro fertilization by donor.

Conclusions: Chromosomal analysis rarely yields 46,XX karyotype combined with no deletion of AZF in infertile males. Under this condition, molecular analysis should be conducted to avoid potential misdiagnosis and false interpretation of other findings.

Keywords: 46,XX disorders of sex development, azoospermia factor, misdiagnosis, mosaicism, sex-determining region Y.