黄体期应用来曲唑和GnRH拮抗剂对OHSS预防作用的随机对照试验

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome:a randomized controlled trial

目的探讨和比较黄体期应用来曲唑和促性腺激素释放激素(GnRH)拮抗剂在卵巢过度刺激综合征(OHSS)高危患者中的预防效果及与生殖激素水平的关系。方法采用前瞻性随机对照试验,将2018年3月至2018年10月在沈阳市妇婴医院生殖中心实施体外受精-胚胎移植或卵母细胞胞质内单精子注射法-胚胎移植(IVF-ET/ICSI-ET)治疗且行全胚胎冷冻的OHSS高危患者99例,按随机数字表随机分成来曲唑组(51例,自取卵日起连续3 d口服来曲唑7.5 mg)和GnRH拮抗剂组(48例,自取卵日起连续3 d皮下注射醋酸西曲瑞克0.25 mg)。观察两组患者早发型OHSS的发生情况,同时测定两组患者取卵后第3、5、8天血清生殖激素(雌二醇、孕酮、LH)水平。结果(1)来曲唑组患者的中~重度OHSS发生率为11.8%(6/51),GnRH拮抗剂组为10.4%(5/48),两组比较,差异无统计学意义(P=0.830)。(2)来曲唑组取卵后第3、5、8天血清雌二醇水平分别为(1417±3543)、(1692±4330)和(239±336)pmol/L,显著低于GnRH拮抗剂组的(15210±9921)、(18680±11567)和(3582±5427)pmol/L,分别比较,差异均有统计学意义(P均<0.01);血清LH水平分别为(0.46±0.40)、(0.56±0.55)和(0.67±0.58)U/L,显著高于GnRH拮抗剂组的(0.28±0.28)、(0.30±0.19)和(0.45±0.37)U/L,差异均有统计学意义(P均<0.05);血清孕酮水平与GnRH拮抗剂组同时间点分别比较,差异均无统计学意义(P均>0.05),但两组第8天的孕酮水平与第3、5天相比均明显下降(P<0.05)。结论黄体期应用来曲唑与GnRH拮抗剂疗效一致,均能降低中~重度OHSS的发生率,且来曲唑口服使用更加便捷,较GnRH拮抗剂费用低廉,但其作用效果可能与生殖激素的下降水平无关。

Objective To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone(GnRH)antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome(OHSS).Methods A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group(n=51)received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group(n=48)were given cetrorelix of 0.25 mg subcutaneously daily for 3 days.Both groups received support therapy combined with embryo cryopreservation.The incidence of OHSS was surveyed.And the serum concentration of estradiol,LH and progesterone on days 3,5 and 8 after oocytes retrieval were measured.Results There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group[11.8%(6/51)]and GnRH antagonist group[10.4%(5/48);P>0.05].The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were(1417±3543)versus(15210±9921)pmol/L,(1692±4330)versus(18680±11567)pmol/L,(239±336)versus(3582±5427)pmol/L,respectively;compared with GnRH antagonist group,the estradiol level was significantly lower in the letrozole group(all P<0.01).The luteinizing hormone level in the letrozole group were(0.46±0.40),(0.56±0.55)and(0.67±0.58)U/L on days 3,5 and 8 after oocytes retrieval,which were significantly higher than those of GnRH antagonist group[(0.28±0.28),(0.30±0.19)and(0.45±0.37)U/L,respectively;all P<0.05].There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group(all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval(P<0.05).Conclusion Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS,faster and cheaper to use,but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.