促性腺激素释放激素激动剂扳机对卵巢过度刺激综合征高风险患者临床结局影响及其相关机制研究

Evaluation of GnRH-a induced ovulation in OHSS-risk patients and analysis of the relevant mechanism

目的评估促性腺激素释放激素激动剂(Gn RH-a)扳机对卵巢过度刺激综合征(OHSS)高风险患者临床结局的影响及其相关机制。方法回顾性分析2015年1-12月广州医科大学附属第三医院生殖医学中心96例OHSS高风险患者,其中Gn RH-a单扳机(48例)和重组人绒毛膜促性腺激素(r-HCG)扳机(48例)应用于患者的体外受精(IVF)周期,并对其中28例患者的颗粒细胞卵丘扩展基因肿瘤坏死因子诱导基因6蛋白(TNFAIP6)和透明质酸合成酶2(HAS2)的表达水平进行分析。结果两组患者年龄、不孕因素、基础内分泌情况、扳机日雌二醇水平、16 mm卵泡数、获卵数、卵裂率、优胚率差异均无统计学意义。与r-HCG扳机相比,Gn RH-a单扳机方案可将OHSS发生率降至0,且能获得更高的受精率(90.22%vs.85.97%,P=0.003)和卵子利用率(44.48%vs.39.34%,P=0.020)。Gn RH-a扳机使颗粒细胞TNFAIP6和HAS2 m RNA的表达明显增高(1.40±0.16 vs.1.00±0.12,P=0.043;1.69±0.23 vs.1.00±0.20,P=0.030)。结论 Gn RH-a扳机方案应用在高反应人群安全有效。Gn RH-a扳机方案中更高的受精率和卵子利用率可能与颗粒细胞上TNFAIP6和HAS2 m RNA的表达增高有关。

Objective To evaluate the clinical outcomes of GnRH-a trigger scheme when applied to OHSS-risk patients and further to analyze the related mechanism.Methods The current study retrospectively reviewed 96 IVF cycles which were applied GnRH-a trigger scheme （n=48） or r-HCG trigger scheme （n=48） in high responders for oocytes maturation and further explored the expressions of cumulus expansion related genes TNFAIP6 and HAS2 in granulosa cells from 28 of those high responders.Results No statistical difference was found in age, infertile factors, basic endocrine profile, serum E2 levels and the number of follicles that reached 16 mm on day of trigger, the number of retrieved oocytes, cleavage rate, high-qualified embryo rate between two groups. GnRH-a trigger scheme could not only reduce the incidence of OHSS to 0, but also obtain better fertilization rate （90.22% vs. 85.97%, P=0.003） and ooeytes available rate （44.48% vs. 39.34%, P=0.020）. On the other hand, TNFAIP6 and HAS2 mRNA expressed significantly higher after GnRH- a trigger treatment （ 1.40± 0.16 vs. 1.00± 0.12, P=0.043 ; 1.69 ± 0.23 vs. 1.00 ± 0.20, P=0.030）. Conclusion It is safe and effective to apply GnRH-a trigger scheme to high responders. It may improve the fertilization rate and embryo quality through up-regulation of the mRNA expressions of TNFAIP6 and HAS2 in granulosa cells.