Testis Development and Fertility Potential in Boys with Klinefelter Syndrome

Abstract

Synopsis Klinefelter syndrome (KS) is the leading genetic cause of primary hypogonadism and infertility in men.1,2 The clinical phenotype has expanded beyond the original description of infertility, small testes and gynecomastia.3 Animal models, epidemiological studies, and clinical research of males with KS throughout the lifespan have allowed us to better characterize the variable phenotype of this condition. This review will provide an overview on what is known of the epidemiology, clinical features, and pathophysiology of KS, followed by a more focused discussion of testicular development and the clinical management of hypogonadism and fertility in men with KS.

The Klinefelter syndrome: current management and research challenges

“…While attempts are being made to obtain and preserve testicular spermatozoa from adolescent KS patients, Joachim Wistuba also addressed approaches to cryopreserve testicular tissues from KS boys and adolescents who are not presenting with testicular gametes (Davis et al, 2015;Gies et al, 2016). Thus, medicine is making a promise that those tissues could offer an option for in vitro differentiation in 20 years, when such boys might have the wish to become fathers.…”

A Klinefelter boy with congenital adrenal hyperplasia: too much or too little androgens?

“…It is the clinical result of an additional X chromosome in males (47,XXY), although other chromosome abnormalities (such as 46,XY/47,XXY mosaicism; 48,XXXY; 49,XXXXY) account for 10–20% of cases. Virtually all men with KS have infertility and small testes with hypergonadotropic hypogonadism [4, 5]. …”

Advances in the Interdisciplinary Care of Children with Klinefelter Syndrome

“…7 Injections have been used for decades and most endocrinologists are familiar with their use. Injections can be given at home or in the primary care physician’s office and dosing is typically titrated based on symptomatology and psychical examination.…”

“…Nearly all untreated men with non-mosaic KS will have elevated LH and FSH, with low or low-normal testosterone and low or undetectable inhibin B and AMH. 7 Testosterone replacement should be offered to all men with evidence of hypergonadotropic hypogonadism even if they are asymptomatic, as many manifestations of gonadal insufficiency may be subtle. The Endocrine Society has published guidelines for testosterone replacement in men with hypogonadism.…”

“…5 Optimizing testosterone treatment may prevent some of the physical manifestations of the “classic KS phenotype.” 6 Advanced Reproductive Technology (ART) has made it possible for nearly half of men with KS previously deemed infertile to have an opportunity to have a biological child. 7,8 Despite these scientific advances, the underlying molecular mechanisms underlying primary testicular failure and the phenotypic heterogeneity of physical and neurocognitive features observed in KS remains elusive. In this review, we will provide the pediatrician with an update on what is known about the clinical manifestations and current treatment recommendations for boys and men with KS.…”