国产注射用重组人卵泡刺激素在不同卵巢储备功能患者长方案控制性超促排卵中的疗效观察

Effectiveness of domestic recombinant follicle stimulating hormone in the course of controlled ovarian hyperstimulation using long protocol in patients with different ovarian reserve function

目的探讨国产注射用重组人卵泡刺激素(rFSH)在不同卵巢储备功能患者长方案控制性促排卵中的效果。方法回顾性分析烟台毓璜顶医院生殖科自2016年1月至2018年1月行体外受精/卵胞浆内单精子注射-胚胎移植治疗的患者共1284例,所有患者均采用标准长方案促排卵,按其抗苗勒管激素(AMH)水平分为卵巢储备正常组(AMH 1.2~4.5μg/L,678例)及高反应组(AMH>4.5μg/L,606例),每组患者按照启动日促性腺激素用药的不同分为国产rFSH组(卵巢储备正常组340例、高反应组330例)与进口rFSH两个亚组(卵巢储备正常组338例、高反应组276例),两两比较不同卵巢储备功能下两亚组患者促排卵后临床及实验室指标。结果不论卵巢储备功能正常或高反应,两亚组患者在促性腺激素(Gn)用量[(1983.15±510.00)U vs.(1913.32±422.12)U,P=0.053;(1816.86±506.37)U vs.(1786.63±453.90)U,P=0.44]、Gn天数[(8.96±1.33)d vs.(8.87±1.24)d,P=0.36;(9.45±1.51)d vs.(9.44±1.47)d,P=0.91]、注射用高纯度尿促性素用药量[(144.20±67.39)U vs.(143.42±56.73)U,P=0.86;(149.52±62.38)U vs.(160.21±84.87)U,P=0.09]、获卵数目[(8.14±3.57)个vs.(8.44±3.37)个,P=0.25;(11.47±4.74)个vs.(11.66±4.49)个,P=0.62]、MⅡ卵子率(82.08%vs. 82.01%,P=0.96;82.78%vs. 82.94%,P=0.90)、受精率(82.17%vs. 80.98%,P=0.30;80.75%vs. 82.16%,P=0.33)、卵裂率(94.55%vs. 93.92%,P=0.52;94.12%vs. 94.84%,P=0.49)、囊胚形成率(58.43%vs. 59.55%,P=0.69;61.14%vs. 63.09%,P=0.46)、临床妊娠率(59.49%vs. 56.54%,P=0.54;62.84%vs. 58.70%,P=0.57)、早期流产率(7.36%vs. 6.80%,P=0.42;11.30%vs. 11.11%,P=0.93)及中重度卵巢过度刺激综合征(OHSS)发生率(3.53%vs. 4.73%,P=0.71;7.58%vs. 9.06%,P=0.53)之间差异均无统计学意义,但国产rFSH组患者hCG日促黄体生成素(LH)水平均较进口rFSH组明显升高[(2.83±1.31)U/L vs.(2.49±1.14)U/L,P=0.007;(2.35±1.10)U/L vs.(2.11±0.94)U/L,P=0.005]。在卵巢储备正常组国产rFSH组hCG日E2浓度及1.6cm以上卵泡数更低,但优胚率显著增高(67.23%vs. 62.51%,P=0.038),差异有统计学意义。结论国产rFSH与进口rFSH长方案促排卵后具有相同的临床妊娠结局,但国产rFSH促排卵后hCG日LH浓度更高,卵巢储备正常患者应用国产rFSH后具有更高的优胚率。

Objective To explore the effect of domestic recombinant follicle stimulating hormone(rFSH)in the course of controlled ovarian hyperstimulation using long protocol in patients with different ovarian reserve functions.Methods A retrospective cohort study was made on 1284 patients who were treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer with standard long protocol for ovulation induction from January 2016 to January 2018 in Reproductive Medicine Center,Yuhuangding Hospital of Yantai.According to their AMH level,they were divided into normal ovarian reserve group(AMH:1.2-4.5μg/L,678 patients)and high response group(AMH>4.5μg/L,606 patients).Each group was divided into domestic rFSH subgroup(Jinsaiheng)(340 patients in normal ovarian reserve group,330 patients in high response group)and imported rFSH subgroup(338 patients in normal ovarian reserve group,276 patients in high response group)according to the different use of gonadotrophin on the start-up day.The clinical and laboratory indexes of the two subgroups were compared under different ovarian reserve functions.Results Regardless of normal or high ovarian reserve function,there was no significant difference in Gn dosage[(1983.15±510.00)U vs.(1913.32±422.12)U,P=0.053;(1816.86±506.37)U vs.(1786.63±453.90)U,P=0.44],days of Gn[(8.96±1.33)days vs.(8.87±1.24)days,P=0.36;(9.45±1.51)days vs.(9.44±1.47)days,P=0.91],dosage of Hermetic[(144.20±67.39)U vs.(143.42±56.73)U,P=0.86;(149.52±62.38)U vs.(160.21±84.87)U,P=0.09],number of eggs obtained(8.14±3.57 vs.8.44±3.37,P=0.25;11.47±4.74 vs.11.66±4.49,P=0.62),MⅡoocyte rate(82.08%vs.82.01%,P=0.96;82.78%vs.82.94%,P=0.90),fertilization rate(82.17%vs.80.98%,P=0.30;80.75%vs.82.16%,P=0.33),cleavage rate(94.55%vs.93.91%,P=0.52;94.12%vs.94.84%,P=0.49),blastocyst formation rate(58.43%vs.59.55%,P=0.69;61.14%vs.63.09%,P=0.46),clinical pregnancy rate(59.49%vs.56.54%,P=0.54;62.84%vs.58.70%,P=0.57),early abortion rate(7.36%vs.6.80%,P=0.42;11.30%vs.11.11%,P=0.93)or the incidence of moderate to severe ovarian hyperstimulation syndrome(OHSS)(3.53%vs.4.73%,P=0.71;7.58%vs.9.06%,P=0.53)between the two subgroups.However,the daily LH level of HCG in domestic rFSH group was significantly higher than that in imported rFSH group[(2.83±1.31)U/L vs.(2.49±1.14)U/L,P=0.007;(2.35±1.10)U/L vs.(2.11±0.94)U/L,P=0.005].In the normal ovarian reserve group,the daily E2 concentration of HCG and the number of follicles above 1.6 cm in the domestic rFSH group were lower,but the rate of good quality embryos was significantly higher(67.23%vs.62.51%,P=0.038),the difference being statistically significant(P=0.038).Conclusion Domestic rFSH has the same clinical pregnancy outcome as imported rFSH after ovulation induction,but domestic rFSH has higher LH concentration on hCG day after ovulation induction,and patients with normal ovarian reserve have higher good quality embyro rate after using domestic rFSH.