Navot D, Rosenwaks Z, Anderson F, Hodgen G D
Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk.
Fertil Steril. 1991 Jun;55(6):1069-75. doi: 10.1016/s0015-0282(16)54354-4.
To determine whether low (subtherapeutic) doses of gonadotropin-releasing hormone agonists (GnRH-a) can cause ovarian hyperstimulation.
The study is in two parts: a preliminary clinical trial of women and a follow-up study in laboratory primates.
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.
Gonadotropin-releasing hormone agonists were administered at subtherapeutic doses.
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.
The data in women and monkeys suggest that a highly individualized response to low GnRH-a doses can be manifested as ovarian hyperstimulation.
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.
确定低（亚治疗）剂量的促性腺激素释放激素激动剂（GnRH-a）是否会引起卵巢过度刺激。
该研究分为两部分：对女性进行初步临床试验以及对实验灵长类动物进行后续研究。
在学术研究环境中对正常人类志愿者进行研究；灵长类动物在常规实验室环境中。
患者、参与者：根据明显的健康状况选择人类志愿者。这些猴子被认为处于正常生殖状态。
以亚治疗剂量给予促性腺激素释放激素激动剂。
在观察到五名接受低剂量GnRH-a的女性中有两名出现卵巢过度刺激后，专门设计了一项研究来检验以下假设：在低（亚治疗）剂量的GnRH-a作用下，“flare效应”可以持续而不发生下调。
女性和猴子的数据表明，对低剂量GnRH-a的高度个体化反应可表现为卵巢过度刺激。
提出四点解释：（1）亚治疗剂量的GnRH-a可引起卵巢过度刺激及相关后遗症；（2）这可能是一个独特的观察结果，因为通常较低剂量的药物副作用发生率较低；（3）研究结果表明，自我给药方案中开具的GnRH-a在不依从的患者中可能更容易出现此类问题；（4）卵巢对低剂量GnRH-a的过度刺激反应可能表明一种新的控制性排卵诱导方法，尽管存在广泛的个体差异。
