Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent implantation and pregnancy rates

Abstract

Objective: To assess the effect of pretreatment with an oral contraceptive (OC) on ovarian cyst formation during pituitary suppression with buserelin acetate.

Design: Prospective randomized trial.

Setting: Academic medical center.

Patient(s): Eighty-three patients who were undergoing IVF-ET treatment.

Intervention(s): Patients in the study group were pretreated with an OC for 14 days starting on the first day of menstruation. The administration of SC buserelin acetate was initiated on the last day of OC administration. Patients in the control group began to receive buserelin acetate on day 2 of menstruation. Hormonal assays and ultrasound scans were performed on the first day of menstruation, and 7, 11, and 14 days after the commencement of buserelin acetate administration. Thereafter, these tests were performed weekly until pituitary suppression was achieved.

Main outcome measure(s): Incidence of cyst formation.

Result(s): A cyst developed in 27 patients in the control group (52.9%) and no patients in the study group (odds ratio [OR]=115; 95% confidence interval [CI]=10-617). Patients in the study group achieved pituitary suppression faster (median difference [MD]=7 days; 95% CI=4-14) and required fewer ampules of gonadotropin (MD=10; 95% CI=6-14). They recruited more follicles (MD=3; 95% CI=0-5) and had higher pregnancy rates (37.2% versus 33.3%).

Conclusion(s): Pretreatment with an OC abolishes ovarian cyst formation, shortens the time required to achieve pituitary suppression, and decreases gonadotropin requirements without having a negative effect on pregnancy rates.

PIP: Administration of a gonadotropin-releasing hormone analog (GnRH-a) before ovarian stimulation with gonadotropins in women undergoing in vitro fertilization (IVF) treatment produces higher pregnancy and live birth rates, but also results in formation of ovarian cysts that must be treated before stimulation can commence. The effect of pretreatment with an oral contraceptive (OC) on ovarian cyst formation during pituitary suppression with the GnRH-a buserelin acetate was investigated in a prospective randomized trial of women undergoing IVF at Royal Victoria Hospital (Montreal, Quebec, Canada). 51 women were pretreated with an OC for 14 days, starting on the first day of menstruation, and began buserelin acetate (500 mcg/day) on the last day of OC administration. The 51 women in the control group were treated with the standard protocol of 500 mcg/day of buserelin acetate starting on the second day of menstruation. A cyst developed in 27 controls (52.9%) but in no women pretreated with OCs (odds ratio, 115; 95% confidence interval, 10.7-617.5). 49 pretreated women (96.1%) compared with 22 controls (43.1%) achieved pituitary suppression after 7 days of GnRH-a administration. Pretreated women also required a median of 10 fewer ampules of gonadotropin than controls, recruited a median of 3 more follicles than their non-pretreated counterparts, and had higher pregnancy rates (37.2% and 33.3%, respectively). OCs are assumed to prevent the formation of ovarian cysts during GnRH-a administration through a dual effect of pituitary suppression and ovarian protection. OC pretreatment enables a significant simplification of the long standard protocol of GnRH-a administration.