两种钙离子载体A23187和离子霉素对卵母细胞激活效果的比较

Effects of artificial oocyte activation with A23187 versus ionomycin on clinical outcomes

目的:比较两种不同钙离子载体A23187和离子霉素对卵母细胞的受精率、胚胎发育潜能和临床结局的影响。方法:采用回顾性队列研究方法,收集2010年5月至2019年12月期间在中山大学附属第六医院生殖医学研究中心、因既往卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)受精失败/受精率低或严重少弱畸形精子症而采用A23187或离子霉素行人工卵母细胞激活(artificial oocyte activation,AOA)的65名患者资料。根据激活剂的不同分为A23187-AOA组和离子霉素-AOA组;再根据不同精子来源分为两个亚组:射出精子组和睾丸精子组比较组间的受精率、胚胎发育潜能及临床结局。结果:离子霉素-AOA组的双原核(two pronuclei,2PN)受精率[55.0%(116/211)]、2PN卵裂率[97.4%(113/116)]及囊胚形成率[69.1%(38/55)]均显著高于A23187-AOA组[43.3%(135/312),P=0.008;90.4%(122/135),P=0.023;45.2%(14/31),P=0.029]。在射出精子组,离子霉素-AOA组的2PN卵裂率[97.1%(68/70)]、第3日(day 3,D3)可移植胚胎率[92.6%(63/68)]均显著高于A23187-AOA组[85.8%(91/106),P=0.013;73.6%(67/91),P=0.002];在睾丸精子组,离子霉素-AOA组的2PN受精率[55.4%(46/83)]、囊胚形成率[93.3%(14/15)]、种植率[38.9%(7/18)]和累积临床妊娠率[66.7%(6/9)]均显著高于A23187-AOA组[37.7%(29/77),P=0.024;20.0%(1/5),P=0.005;5.6%(1/18),P=0.041;10.0%(1/10),P=0.019]。入组的65名患者共活产婴儿20例,均未见出生缺陷与先天畸形。结论:对于因既往ICSI受精失败/受精率低或严重少弱畸形精子症行AOA的患者,离子霉素可以获得比A23187更好的受精率及胚胎发育潜能;对于睾丸来源的严重少弱畸形精子,与A23187相比,离子霉素可以令患者获得更好的临床结局。

Objective To compare the fertilization rate,embryonic developmental potential,and clinical outcomes following the applications of A23187 and Ionomycin.Methods A total of 65 patients whose oocytes were exposed to either the A23187 or Ionomycin for artificial oocyte activation(AOA)due to total failed fertilization/lower fertilization rate in the previous intracytoplasmic sperm injection(ICSI)cycles or severe oligo-astheno-teratozoospermia at Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University from May 2010 to December 2019 were enrolled in this retrospective cohort study.All patients were categorized into two groups:A23187-AOA group and Ionomycin-AOA group.And each group was divided into two subgroups according to sperm origin(ejaculated or testicular sperm).The fertilization rate,embryo development potential and clinical outcome were compared between the two groups.Results The two pronuclei(2PN)fertilization rate[55.0%(116/211)vs.43.3%(135/312),P=0.008],2PN cleavage rate[97.4%(113/116)vs.90.4%(122/135),P=0.023]and blastocyst formation rate[69.1%(38/55)vs.45.2%(14/31),P=0.029]in the Ionomycin-AOA group were significantly higher than those in the A23187-AOA group.In the ejaculated spermatozoa subgroup,the 2PN cleavage rate[97.1%(68/70)vs.85.8%(91/106),P=0.013]and the rate of day 3(D3)transferable embryos[92.6%(63/68)vs.73.6%(67/91),P=0.002]in the Ionomycin-AOA group were higher than those in the A23187-AOA group;in the testicular spermatozoa subgroup,the 2PN fertilization rate[55.4%(46/83)vs.37.7%(29/77),P=0.024],the blastocyst formation rate[93.3%(14/15)vs.20.0%(1/5),P=0.005],the implantation rate[38.9%(7/18)vs.5.6%(1/18),P=0.041]and the cumulative clinical pregnancy rate[66.7%(6/9)vs.10.0%(1/10),P=0.019]in the Ionomycin-AOA group were higher than those in the A23187-AOA group.A total of 20 healthy neonates were delivered in 65 patients.None of the congenital anomalies(birth defects)was found in fetuses after AOA.Conclusion Ionomycin may be superior to A23187 for improving fertilization rate and embryonic developmental potential.And compared with A23187,Ionomycin may be a more efficient means to benefit the patients with testicular-origin severe oligo-astheno-teratozoospermia.