The genophage was a biological weapon deployed against the krogan by the turians during the Krogan Rebellions. It was designed to severely reduce krogan numbers by "infecting" the species with a genetic mutation.
The genophage's modus operandi is not to reduce the fertility of krogan females, but rather the probability of viable pregnancies: many krogan die in stillbirth, with most fetuses never even reaching this stage of development. Moreover, every cell in each krogan is infected, to prevent the use of gene therapy to counteract it. Though the genophage was not designed as a "sterility plague", the combination of a low frequency of viable pregnancies with the krogan proclivity to violence and indifference about focused breeding leaves the krogan a dying race, and soon to be extinct.
The genophage was originally developed by the salarians. They believed that, as the consequences would be so devastating, no one would ever deploy the genophage, thus wielding it as a deterrent. However, the salarians and the turians had different military attitudes, the turians only appreciating an approach of "massive retaliation". Once the genophage was complete, the turians immediately used it, and krogan numbers began to dwindle rapidly. Any female krogan who could carry young to term became a prize of war who was viciously fought over. Taking advantage of this, a female warlord named Shiagur used her fertility as a bargaining chip to attract the strongest males to her army.
After several hundred years of living with the genophage, the knowledge their species will soon be extinct has created a kind of fatalism amongst the krogan that makes them dangerous opponents—they are indifferent to who they attack or kill, or what risks they take, as their species is doomed. A few individuals, such as Wrex, have attempted to rebuild the species, or at least curtail its decline, by focusing on breeding, but the inherent belligerence of the krogan usually frustrates their efforts. There is no known cure for the genophage. Some krogan groups have invested in companies such as Binary Helix to try to discover one; however, efforts have so far been thwarted by a lack of krogan scientists and a disinterest of other species in a revived krogan population. This has led to some krogan trying bizarre alternatives: as Garrus Vakarian informs an incredulous Commander Shepard, there is a healthy trade in krogan testicles on the black market, because of the unsubstantiated belief that testicle transplants can counteract the effects of the genophage.