Incorporation of a GnRH agonist, leuprolide acetate, into regimens with exogenous gonadotropins to produce ovarian stimulation and ovulation in the nonpregnant squirrel monkey

This study was designed to measure the effects of variations in the length of pretreatment with a GnRH agonist, leuprolide acetate (LA), on subsequent follicular development and ovulation. The hypothesis was that the duration of LA suppression of pituitary function does not adversely affect ovarian response to standardized ovulation induction protocols in squirrel monkeys. The first phase determined the dose and duration of LA needed to achieve a hypogonadal state. One of two groups received daily subcutaneous injections of 50 μg of LA. The other received a single injection of 175 μg of a depot suspension of LA. Sera were assayed for estradiol (E2) and progesterone (P). E2 and P levels increased 2‐ to 5‐fold with peak levels on days 4 and 7, respectively. Suppression of steroid levels took 10 to 15 days in the LA‐treated group. Depot‐LA did not effectively suppress steroid production. After suppression, females receiving daily LA received five daily injections of hMG to stimulate follicular development. E2 and P increased in these animals. These results suggest that cycling squirrel monkeys have P‐secreting capacity throughout the cycle. This may explain how the squirrel monkey is able to accommodate both a short (4–5 day) luteal phase of their 9 day cycle and implantation from 5 to 7 days after ovulation. A second study compared exogenous follicle stimulating hormone (FSH) to endogenous gonadotropins released as a response to LA in ovulation induction. Steroid production and hCG‐induced ovulation were assessed. LA treatment was compared to a standard ovulation induction protocol by using a randomized cross‐over measures design. There were no differences in E2 and P levels in response to dosages of either LA or hMG. The ovulatory response following LA treatment was not significantly greater than that using FSH. The number of animals with unovulated, large follicles was greater on the FSH protocol (12/18) compared to the LA protocol (3/18). Thus, a single injection of a depot preparation of LA is sufficient to stimulate follicular development and ovulation when followed by an hCG injection. Based on this observation and the data on unovulated large follicles, it is suggested that the ovary responds more readily to endogenous gonadotropins released by LA than to exogenous FSH. Am. J. Primatol. 49:153–164, 1999. © 1999 Wiley‐Liss, Inc.