三种促排卵方案在卵巢低反应患者中的应用价值比较

Three ovarian stimulation protocols for infertile patients with poor ovarian response

背景卵巢低反应(poor ovarian response,POR)患者的管理和治疗一直是辅助生殖领域中的一个重要问题。目前,有很多促排卵方案应用于卵巢低反应患者,但哪一种促排卵方案最适合POR患者至今没有达成共识。目的本研究旨在比较枸橼酸氯米芬(clomiphene citrate,CC)+注射用尿促性素(human menotropins,HMG)方案、CC+HMG+拮抗剂方案、重组人促卵泡激素(follicle-stimulating hormone,FSH)+拮抗剂方案在POR患者中的应用及临床结局,探讨更适于POR患者的促排卵方案。方法回顾性分析2017年1月-2019年12月于解放军总医院第一医学中心行体外受精/卵胞浆单精子显微注射治疗的POR患者,共纳入279个促排周期,按照促排卵方案分组:A方案组(CC+HMG方案,42个周期),B方案组(CC+HMG+拮抗剂方案,154个周期),C方案组(FSH+拮抗剂方案,83个周期)。比较三组促性腺激素(gonadotropins,Gn)用量、Gn使用时间、扳机日促黄体生成素(leuteinzing hormone,LH)水平、早发LH峰发生率、周期取消率、获卵数、卵裂数、优质胚胎数和临床妊娠率等指标。结果三组患者年龄、不孕年限、基础促卵泡生成素(basal follicle-stimulating hormone,bFSH)、基础促黄体生成素(basal leuteinzing hormone,bLH)、窦卵泡数(antral follicle count,AFC)、体质量指数(body mass index,BMI)差异无统计学意义(P>0.05)。Gn用量(IU)C组最多(1842.47±538.95),B组次之(551.79±182.85),A组最少(450.00±151.82);Gn使用时间(d)C组最长(8.51±1.59),B组次之(7.08±2.09),A组最短(6.00±2.02);扳机日LH水平(IU/L)A组最高(10.41±5.29),B组次之(6.53±3.31),C组最低(3.90±3.01);早发LH峰发生率A组最高(33.3%),B组次之(14.3%),C组最低(2.4%);上述各指标组间差异均有统计学意义(P均<0.05)。周期取消率A组为23.8%,B组和C组无取消周期(P=0.000)。获卵数C组最多(2.58±1.49),显著多于B组(2.01±1.32)和A组(1.94±0.98)(P<0.05)。卵裂数和优质胚胎数三组差异无统计意义(P>0.05)。临床妊娠率A组(13.0%)低于B组(24.5%)和C组(28.8%),但组间差异无统计学意义(P>0.05)。结论对于卵巢低反应患者,CC+HMG+拮抗剂方案较CC+HMG方案的周期取消率低,临床妊娠率高;与FSH+拮抗剂方案相比,CC+HMG+拮抗剂方案Gn用量少、时间短、可重复性高、经济负担小,在临床上值得推荐应用。

Background The management and treatment of patients with poor ovarian response(POR)is still a controversial issue in assisted reproductive technology.Many ovarian stimulation protocols have been applied to patients with POR,however,a consensus upon which is the most beneficial has not been reached yet.Objective To compare the clinical outcomes of three different stimulation protocols(CC+HMG protocol,CC+HMG+antagonist protocol and FSH+antagonist protocol),and explore a better protocol plan for patients with POR.Methods A retrospective analysis was performed in infertile women with poor ovarian response after in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)in the First Medical Center of Chinese PLA General Hospital from January 2017 to December 2019.Data of 279 stimulation cycles were analyzed.The patients were divided into CC+HMG protocol group(group A),CC+HMG+antagonist protocol group(group B)and FSH+antagonist group(group C).The following data,including the dosage and duration of gonadotropin(Gn)use,level of LH on trigger day,rate of premature LH surge,cycle cancellation rate,number of oocytes obtained,number of cleavage embryos and number of high-quality embryos and clinical pregnancy rate were compared between the three groups.Results There was no significant difference in age,duration of infertility,bFSH,bLH,AFC,BMI among the three groups(P>0.05).Gn dosage was highest in group C(1842.47±538.95)IU,followed by the group B(551.79±182.85)IU,and lowest in the group A(450.00±151.82)IU;Gn duration in the group C(8.51±1.59)d was longest,followed by the group B(7.08±2.09)d,and then the group A(6.00±2.02)d;Level of LH on trigger day was highest in the group A(10.41±5.29)U/L,followed by the group B(6.53±3.31)U/L,and lowest in the group C(3.90±3.01)U/L;Rate of premature LH surge was highest in the group A(33.3%),followed by the group B(14.3%),and lowest in the group C(2.4%);The differences in these variables were significant between the three groups(all P<0.05).Rate of cycle cancellation in the group A was 23.8%,which was significantly higher than that in the group B(0)and C(0)(P=0.000).Number of oocytes obtained in the group C(2.58±1.49)was significant greater than that in the group B(2.01±1.32)and the group A(1.94±0.98)(P<0.05).But the number of cleavage embryos and high-quality embryos were similar in the three groups(P>0.05).Clinical pregnancy rate in the group A(13.0%)was lower than that in the group B(24.5%)and C(28.8%),without statistically significant difference(P>0.05).Conclusion For infertile women with POR,the CC+HMG+antagonist protocol is better than CC+HMG protocol,as the former protocol has lower cycle cancellation rate and higher clinical pregnancy rate.Compared with FSH+antagonist protocol,the CC+HMG+antagonist protocol almost has the same clinical pregnancy rate but lower dosage of gonadotropin and shorter duration.Furthermore,patients used CC+HMG+antagonist protocol usually cost less and repeat more ovarian stimulation cycles during the same period.In conclusion,the CC+HMG+antagonist protocol is recommended for infertile patients with POR.