Gustofson Robert L, Segars James H, Larsen Frederick W
Reproductive Endocrinology and Infertility, NIH, Bethesda, MD, USA.
Hum Reprod. 2006 Nov;21(11):2830-7. doi: 10.1093/humrep/del059. Epub 2006 Sep 11.
Elevated estradiol (E(2)) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels and avoid cycle cancellation.
Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage.
In the treatment group, there was a significant, reproducible reduction in serum E(2) levels. Mean E(2) at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy.
GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E(2) without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS.
雌二醇(E₂)水平升高易引发卵巢过度刺激综合征(OHSS)。由于促性腺激素释放激素(GnRH)拮抗剂与E₂水平降低有关,我们推测,对有OHSS风险且已用GnRH激动剂进行降调节的女性采用GnRH拮抗剂治疗,可能会降低E₂水平并避免取消周期。
在一所大学的辅助生殖技术(ART)项目中进行回顾性研究,87例接受长效黄体期(LL)或微剂量激发(MDF)方案且卵巢反应过度的患者以及87例无卵巢过度反应的对照患者纳入研究。对那些对促性腺激素剂量减少无反应的女性开始使用GnRH拮抗剂(醋酸加尼瑞克)治疗,并停用醋酸亮丙瑞林。
治疗组血清E₂水平出现显著且可重复的降低。加尼瑞克治疗开始时E₂的平均水平为4219.8 pg/ml,24小时内降至2613.7 pg/ml(降低36.7%;P < 0.001)。取卵时平均获得24.9 ± 8.8个卵母细胞,其中平均19.1 ± 8.0个处于中期Ⅱ(79.2%)。13.9 ± 8.1个胚胎发生受精(72.8%)。在这个高风险组中,发生了2例严重OHSS(2.3%)。持续妊娠率为51.8%。与对照组相比,在卵母细胞回收、卵母细胞成熟、2PN率、受精、取消周期、OHSS或妊娠率方面无统计学显著差异。
对先用GnRH激动剂预处理的女性采用GnRH拮抗剂治疗可迅速降低循环血清E₂水平,且不会对卵母细胞成熟、受精率或胚胎质量产生不利影响,在这个有OHSS风险的患者亚组中导致了较高的妊娠率。