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Gonadotropin-releasing hormone agonist-induced ovarian hyperstimulation: low-dose side effects in women and monkeys
D Navot1, Z Rosenwaks, F Anderson
1Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk.
Objective:
To determine whether low (subtherapeutic) doses of gonadotropin-releasing hormone agonists (GnRH-a) can cause ovarian hyperstimulation.
Design:
The study is in two parts: a preliminary clinical trial of women and a follow-up study in laboratory primates.
Setting:
Normal human volunteers were studied in an academic research environment; primates were in a conventional laboratory setting.
Patients, Participants:
Human volunteers were selected on the basis of apparent normal health. The monkeys were believed to be of normal reproductive status.
Interventions:
Gonadotropin-releasing hormone agonists were administered at subtherapeutic doses.
Main Outcome Measures:
After observing ovarian hyperstimulation in two of five women receiving low doses of GnRH-a, a study was specifically designed to test the hypothesis that at low (subtherapeutic) doses of GnRH-a the "flare-effect" can be sustained without achieving down regulation.
Results:
The data in women and monkeys suggest that a highly individualized response to low GnRH-a doses can be manifested as ovarian hyperstimulation.
Conclusion:
Four points of interpretation are offered: (1) that subtherapeutic doses of GnRH-a can cause ovarian hyperstimulation and related sequelae; (2) this may be a unique observation in that, typically, lower doses of medications have a lower incidence of negative side effects; (3) the findings suggest that GnRH-a prescribed in self-administration regimens may be more prone to such problems in noncompliant patients; and (4) the hyperstimulation response of the ovaries to low GnRH-a doses may indicate a new approach to controlled ovulation induction, although wide individualism was found.