ABSTRACT
In order to understand the modern approach to induction of ovulation by gonadotropins, one should know something of the history of this type of treatment. Induction of ovulation by gonadotropins has been practiced since the 1950s. Gemzell and co-workers were the first to publish results;1 this was in 1958, even before Greenblatt published his first paper on induction of ovulation by clomiphene citrate.2 This therapy had early difficulties, mainly because of the lack of therapeutic material. Gemzell originally worked with human pituitary follicle-stimulating hormone (FSH), a material that was later on used almost exclusively by the British and the Australians. In Europe and especially in Israel, use was made of human menopausal gonadotropins (hMG), extracted from the urine of postmenopausal women.3 The side effects of this therapy, i.e. the ovarian hyperstimulation syndrome and the occurrence of multiple pregnancies, soon became evident. It was Brown who was the first to conclude that because of these side effects clomiphene citrate was the drug of choice and that the use of gonadotropins should be restricted to patients
Lunenfeld, Gemzell, Townsend, Evans and Brown, Crooke and others,1,3-9 new techniques were developed, particularly when daily estrogen determinations became available for careful monitoring.10 Consensus on the use of these monitoring techniques was soon reached but remarkable differences existed with respect to the dose schedules. Standard dose schedules were rejected by all, and individualized step-up schedules became the standard. Rabau et al3
recommended starting with one ampule and increasing by one ampule each week, while Brown and co-workers insisted that the increase in dose should never exceed a third of the preceding dose.4
