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Follicle-stimulating hormone (FSH)-containing gonadotropin preparations have been commercially available since the 1960s. Their first use was in ovulation induction in women with anovulatory disorders. Since 1978, however, after the first in vitro fertilization (IVF) baby was born, they have been used increasingly in assisted reproductive technologies (ART) such as IVF or intracytoplasmic sperm injection (ICSI) but also in intrauterine insemination (IUI) as ovarian stimulation to achieve multifollicular growth. Now, in many countries, ovulation induction stimulation comprises only 10% of gonadotropin usage, while 90% is used for ovarian (hyper) stimulation in ART, of which about half of the gonadotropin usage is for IVF and the other half is used for stimulated IUI cycles.
This chapter reviews pharmacological agents with a focus on the clinical aspects of their use. There are two groups of pharmacological agents for ovarian stimulation: the first group includes injectable gonadotropins and the second group includes oral agents that are estrogen modulators. Enclomiphene is the more potent antiestrogenic isomer and the one primarily responsible for the ovulation-stimulation actions of clomiphene citrate (CC). It is important to stress the two main prerequisites for the success of CC ovarian stimulation: presence of reasonable estrogen levels in the body and an intact hypothalamic/pituitary axis capable of producing endogenous gonadotropins. Aromatase activity is present in many normal tissues, such as the ovaries, the brain, muscle, liver, breast tissue, as well as in pathological tissues such as malignant breast tumors. The short half-life of letrozole and absence of estrogen receptor antagonism result in a very favorable profile for infertility treatment compared with CC.