Increasing fertility in a mammal utilizes cationic steroidal antimicrobial (CSA) compounds and CSA-containing compositions. Such treatment in a mammal includes administering a formulation (e.g., lavage and/or infusion) including at least one CSA compound, or pharmaceutically acceptable salt thereof, to the reproductive structure(s) of the mammal (e.g., horse, dairy cow, human, etc.). The formulation may be applied topically as lavage and/or infusion to desired reproductive structures, such as the vagina, cervix, uterus, penis, or combinations thereof. The formulation may kill both planktonic and biofilm forms of sperm killing microbes, and may at least partially break up a microbial plaque or film located within any of the reproductive structures (e.g., the uterus). The CSA or pharmaceutically acceptable salt thereof may be selective or preferential in its action, so as to preferentially kill sperm killing microbes without causing harm to beneficial microbes also residing within the reproductive structure of the mammal.