Fertility in Cystinosis

Abstract

Cystinosis is a rare inheritable lysosomal storage disorder characterized by cystine accumulation throughout the body, chronic kidney disease necessitating renal replacement therapy mostly during adolescence, and multiple extra-renal complications. The majority of male cystinosis patients are infertile due to azoospermia, in contrast to female patients who are fertile. Over recent decades, the fertility status of male patients has evolved from a primary hypogonadism in the era before the systematic treatment with cysteamine to azoospermia in the majority of cysteamine-treated infantile cystinosis patients. In this review, we provide a state-of-the-art overview on the available clinical, histopathological, animal, and in vitro data. We summarize current insights on both cystinosis males and females, and their clinical implications including the potential effect of cysteamine on fertility. In addition, we identify the remaining challenges and areas for future research.

Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients

“…Males with infantile cystinosis were previously thought to be infertile, but some have fathered children through in vitro fertilization (IVF), after percutaneous epididymal sperm aspiration, using their own sperm [ 19 ]. A few male patients with cystinosis were reported to have viable sperm in ejaculate [ 20 ].…”

Fertility Management in Cystinosis: A Clinical Perspective

“…These patients commonly experience delayed puberty; low levels of testosterone; and increased levels of gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone. 12 , 16 Kidney function and treatment with immunosuppressive agents appear to have little influence on the hormonal disturbances in males with cystinosis. 12 Although primary hypogonadism was previously thought to be the prevailing mechanism of infertility, with the advent of cysteamine therapy, infertility in males with cystinosis has more recently been attributed to obstructive azoospermia and has been seen in patients with normal sex hormone levels ( Table 1 ).…”

“… 11 , 16 , 17 Cystinosis has especially significant impacts on male reproductive health, typically leading to infertility due to primary hypogonadism and azoospermia. 12 Females with cystinosis are usually fertile; however, special attention must be given to their renal function, medications, and overall health status during preconception and pregnancy. 18

Figure 1 Impacts on the reproductive health of individuals with cystinosis.

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Figure 1 Impacts on the reproductive health of individuals with cystinosis. 1 , 11 , 12 , 13 , 14 , 15 Delayed puberty, growth failure, hypothyroidism, and renal impairment affect the reproductive health in males and females with cystinosis. By adulthood, males are typically infertile, whereas females have normal fertility but are at high risk for pregnancy complications.

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Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective

“…In the most common and severe form of the disease, patients suffer from complete proximal tubulopathy, named renal Fanconi syndrome, and progress to kidney failure during the first decade of life [ 5 ]. Other organs are also affected including the eyes, thyroid, bones, muscles, pancreas, and gonads [ 6 – 9 ]. The diagnosis can be made by detecting either elevated intra-leukocytes cystine levels (IL-CL), or cystine crystals in the cornea on slit lamp examination, confirmed by genetic testing if possible [ 10 ].…”