Klinefelter syndrome), some cases of cryptorchidism or Sertoli cell-only syndrome as well as acquired conditions by infection (orchitis), surgery (trauma, cancer), radiation, or other causes. Mast cells releasing inflammatory mediators appear to directly suppress sperm motility in a potentially reversible manner, and may be a common pathophysiological mechanism for many causes leading to inflammation. Testicular azoospermia is a kind of non-obstructive azoospermia. Generally, men with unexplained hypergonadotropic azoospermia need to undergo a chromosomal evaluation. Post-testicular
In post-testicular azoospermia, sperm are produced but not ejaculated, a condition that affects 7–51% of azoospermic men. The main cause is a physical obstruction (obstructive azoospermia) of the post-testicular genital tracts. The most common reason is a vasectomy done to induce contraceptive sterility. Other obstructions can be congenital (for example, agenesis of the vas deferens as seen in certain cases of cystic fibrosis) or acquired, such as ejaculatory duct obstruction for instance by infection. Ejaculatory disorders include retrograde ejaculation and anejaculation; in these conditions sperm are produced but not expelled. Unknown
Idiopathic azoospermia is where there is no known cause of the condition. It may be a result of multiple risk factors, such as age and weight. For example, a review in 2013 came to the result that oligospermia and azoospermia are significantly associated with being overweight (odds ratio 1.1), obese (odds ratio 1.3) and morbidly obese (odds ratio 2.0), but the cause of this is unknown. The review found no significant relation between oligospermia and being underweight.
Tumours need blood vessels sprouting into them when they become larger than a few millimetres, in order to get access to oxygen and nutritive substances to facilitate further growth. Aflibercept binds to circulating VEGFs and acts like a "VEGF trap". It thereby inhibits the activity of the vascular endothelial growth factor subtypes VEGF-A and VEGF-B, as well as to placental growth factor (PGF), inhibiting the growth of new blood vessels in the choriocapillaris or the tumour, respectively. The aim of the cancer treatment, so to speak, is to starve the tumour. Composition
Aflibercept is a recombinant fusion protein consisting of vascular endothelial growth factor (VEGF)-binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin. History
Regeneron commenced clinical testing of aflibercept in cancer in 2001. In 2003, Regeneron signed a major deal with Aventis to develop aflibercept in the field of cancer. In 2004 Regeneron started testing the compound, locally delivered, in proliferative eye diseases, and in 2006 Regeneron and Bayer signed an agreement to develop the eye indications.