The CatSper (Cation Channel of Sperm) complex is a sperm-specific calcium channel that controls sperm hyperactivation, a motility pattern required for successful fertilization (1, 2). The CatSper channel is localized in the sperm flagellum and consists of four pore-forming subunits (CatSper 1–4) along with at least 11 auxiliary proteins, making it the most complex ion channel known (3).

CatSper is activated by hormones released by the egg such as progesterone and prostaglandins, triggering an influx of calcium into the flagellum and, thereby, hyperactivated motility (4, 5). In humans, variants in CATSPER genes that lead to the loss of CatSper function cause male infertility – without functional CatSper, sperm cannot fertilize the egg (6–14). However, men with CatSper-related infertility often feature normal sperm production and semen quality (10–14). As a result, they are often diagnosed with “unexplained” infertility and experience failed attempts of medically assisted reproduction by intrauterine insemination (IUI) and conventional in vitro fertilization (IVF). In fact, CatSper-related infertility requires intracytoplasmic sperm injection (ICSI) for conception (10–12, 14).

Men with a homozygous deletion of the CATSPER2 gene often experience mild-to-moderate hearing loss due to the simultaneous loss of the STRC gene, which encodes stereocilin, a protein essential for hearing function (8). This condition, known as Deafness-Infertility Syndrome, arises because CATSPER2 and STRC are located adjacent to each other on chromosome 15. These genes are frequently deleted together as one large segment, despite playing completely unrelated biological roles—one in sperm function and the other in the inner ear (15).

Loss of CatSper function is caused by genetic aberrations rather then lifestyle or environmental factors. So far, genetic variants causing CatSper-related infertility have been identified in the CATSPER1, CATSPER2, CATSPER3, and CATSPERE (epsilon) genes, with CATSPER2 deletions being the predominant cause (10, 14, 15).

Because these variants are inherited in an autosomal recessive manner, genetic testing is recommended to assess reproductive risks for future offspring. Men with CatSper-related infertility will pass on a pathogenic variant, and if their partner carries the same variant, their male offspring may inherit infertility, and both male and female offspring may develop hearing loss if STRC is also affected. Genetic diagnostics and counselling can help determine whether the female partner is a carrier and determine the risk of inheriting infertility or hearing impairment.

The CE-labeled CatFlux Solutions allow any laboratory capable of performing a semen analysis to perform the CatSper-Test, which represent the only in vitro diagnostic method for the detection of CatSper-related infertility. Developed by reproductive scientists and clinicians at the University of Münster in Germany, CatFlux Solutions are a simple, rapid, and reliable tool for performing the CatSper-Test. The early detection of CatSper-related infertility prevents ineffective IUI and IVF cycles and guides clinicians and patients directly towards evidence-based treatment options such as ICSI (10).

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