Filicori M, Flamigni C, Meriggiola M C, Ferrari P, Michelacci L, Campaniello E, Valdiserri A, Cognigni G
Department of Obstetrics and Gynecology, University of Bologna, Italy.
J Clin Endocrinol Metab. 1991 May;72(5):965-72. doi: 10.1210/jcem-72-5-965.
To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. In PCOS, 50 cycles were preceded by GnRH analog suppression. PHA treatment cycles were characterized by the reestablishment of a normal endocrine pattern, almost no dose-related endocrine differences, elevated ovulatory (93%) and conception rates (23%), and no multiple pregnancies. In the HH subjects the ovulatory (91%) and pregnancy rates (31%) were high; however, while the lower GnRH dose elicited a normal endocrine pattern, the 5-micrograms dose induced excessive folliculogenesis and high estradiol levels and was associated with most of the multiple pregnancies of this study (three of four). GnRH analog suppression was successfully used to avoid recurrence of ovarian over-stimulation in two HH subjects. Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction.
为了系统收集不同排卵障碍中内分泌反应、临床结局和并发症发生之间确切关系的信息，我们对114例患者进行了187个周期的脉冲式促性腺激素释放激素（GnRH，2.5 - 5.0微克，静脉注射，每60分钟一次）治疗，并将其与20个正常月经周期进行比较。这些患者中，30例患有原发性低促性腺激素性闭经（PHA；40个周期），33例患有其他形式的低促性腺激素性性腺功能减退（HH；55个周期），51例患有多囊卵巢综合征（PCOS；92个周期）。每天采集血样进行激素测定。在PCOS患者中，50个周期在GnRH类似物抑制后进行。PHA治疗周期的特点是恢复正常内分泌模式，几乎没有剂量相关的内分泌差异，排卵率（93%）和受孕率（23%）升高，且无多胎妊娠。在HH患者中，排卵率（91%）和妊娠率（31%）较高；然而，较低剂量的GnRH可引发正常内分泌模式，而5微克剂量则诱导过度卵泡生成和高雌二醇水平，并与本研究中的大多数多胎妊娠相关（四例中的三例）。GnRH类似物抑制成功用于避免两名HH患者卵巢过度刺激的复发。最后，PCOS患者中的GnRH类似物抑制可使卵泡期内分泌模式正常化，实现良好的排卵率（76%）和妊娠率（28%），并避免多胎妊娠；然而，黄体期类固醇分泌异常，流产率仍然较高（43%）。肥胖与PCOS患者的排卵率降低相关，但在低促性腺激素患者中并非如此。因此，我们可以得出结论，在脉冲式GnRH诱导排卵中：1）严重的低促性腺激素状态，无论是如PHA中的自发性状态还是如其他排卵障碍中用GnRH类似物诱导的状态，都与最佳月经周期恢复、高排卵率和受孕率以及几乎不存在多胎妊娠风险相关；2）HH患者中残留的下丘脑活性可能导致垂体 - 卵巢超生理刺激，并导致多胎妊娠，除非采用低剂量GnRH（2.5微克/推注）或GnRH类似物预处理；3）肥胖不影响低促性腺激素患者的治疗结局；4）PCOS患者中高自然流产率可能与黄体功能不全有关。
