Induction of ovulation and pregnancy with pulsatile luteinizing hormone releasing factor: dosage and mode of delivery.

The efficacy of intravenous and subcutaneous routes for pulsatile delivery of differing dosages of synthetic luteinizing hormone releasing factor (LRF) for ovulation induction were evaluated sequentially in two patients with presumed deficiency of endogenous LRF: isolated gonadotropin deficiency and pituitary stalk transection with hyperprolactinemia. Observations were made of the amplitude and duration of the induced LH-FSH pulses, of follicular growth and ovulation (via ultrasound), and of ovarian steroids. Remarkable differences in each of these parameters were found between the two modes of LRF delivery. LRF pulses administered subcutaneously resulted in inappropriate gonadotropin secretion, arrest of follicular development, elevated ratios of E1/E2 and androgens/estrogens, and the appearance of acne - features of polycystic ovary syndrome. In contrast, the first intravenous course of pulsatile LRF induced orderly follicular maturation and ovulation with subsequent pregnancy in both subjects. From these findings we conclude that, in these patients, the intravenous mode of delivery of LRF pulses was superior to the subcutaneous route at all doses tested.