Embryonic development and clinical outcomes in patients with 0PN zygote derived embryos
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摘要:
目的 未见原核(0PN) 受精卵的受精及胚胎发育异常的病因尚不清楚,其移植的适宜性仍存在争议,本研究旨在探究0PN受精卵是否具有应用价值。 方法 分析2019年9月—2022年5月行体外受精(IVF)/卵胞浆内单精子注射(ICSI)的9 167个周期。(1)比较6 915个周期[每个周期中存在≥1个0PN受精卵,以下简称两原核(2PN)+0PN组]与2 252个周期(每个周期均由2PN受精卵发育而来,以下简称2PN组)的胚胎发育与临床结局。(2)根据0PN衍生胚胎的比例将IVF周期中患者进一步分类为:L组(0~30%,2 579例)、M组(31%~60%,782例)和H组(61%~100%,221例),比较3组的胚胎发育与临床结局。(3)单独比较72个由0PN受精卵发育周期(0PN100%组)与100个由2PN发育周期(2PN100%组)的胚胎发育与临床结局。 结果 (1) 2PN组的囊胚形成率显著高于2PN+0PN组(62.44% vs. 55.01%,P<0.001),2PN组的累计活产率(CLR)显著低于2PN+0PN组(54.97% vs. 64.99%,P<0.001)。2PN+0PN组与2PN组新生儿体重、Apgar评分比较差异均无统计学意义。(2)L、M和H组的获卵数、受精率、累计临床妊娠率(CCR)、CLR呈递减趋势。M组的卵裂率显著高于其余2组;优质胚胎率、囊胚形成率、优质囊胚率显著高于L组。(3)0PN衍生胚胎(0PN100%组)的活产率显著低于2PN衍生胚胎(2PN100%组,30.56% vs. 60.00%,P<0.001),但2组囊胚移植后的临床结局差异均无统计学意义(P>0.05)。 结论 0PN衍生胚胎临床妊娠后,并未观察到流产可能性明显增加或对新生儿健康产生明显负面影响。因此,当无法获得正常囊胚时,0PN衍生胚胎的移植应被视为可行的选择。 Abstract:Objective The cause of abnormal fertilization and embryo development in non-pronucleus (0PN) zygotes remains unclear, and the viability of transferring 0PN zygotes is still controversial. The study aims to explore the clinical utility of 0PN zygote-derived embryos. Methods A total of 9 167 IVF/ICSI cycles conducted between September 2019 and May 2022 were analyzed. (1) Embryo development and clinical outcomes were compared between 6 915 cycles with at least one OPN fertilization (2PN/0PN) and 2 252 cycles with all embryos from 2PN fertilization (2PN group). (2) Patients were further categorized based on the proportion of 0PN-derived embryos in IVF cycles: L group (0-30%, n=2 579), M group (31%-60%, n=782), and H group (61%-100%, n=221), with embryo development and clinical outcomes compared across groups. (3) Embryo development and clinical outcomes were also compared with complete 0PN (0PN 100% group) and complete 2PN (2PN 100% group). Results (1) The blastocyst formation rate of 2PN group was significantly higher than that of the 2PN/0PN group (62.44% vs. 55.01%, P < 0.001), whereas the cumulative live birth rate (CLR) of 2PN group was significantly lower than the 2PN/0PN group (54.97% vs. 64.99%, P < 0.001). There was no significant difference in neonatal weight or Apgar score between the two groups. (2) The number of oocytes retrieved, fertilization rate, cumulative clinical pregnancy rate (CCR), and CLR decreased progressively across L, M, and H. The cleavage rate of group M was significantly higher than that in the other two groups. H group had significantly higher rates of high-quality embryos, blastocyst formation, and top-grade cysts compared to the group L. (3) The live birth rate for 0PN-derived embryos (0PN 100% group) was significantly lower than for 2PN-derived embryos (2PN 100% group, 30.56% vs. 60.00%, P < 0.001), though there was no significant difference in clinical outcomes after blastocyst transfer between the two groups (P>0.05). Conclusion Clinical pregnancy outcomes after transferring 0PN-derived embryos did not show increased risk of miscarriage or adverse neonatal. Therefore, transferring 0PN-derived embryos may be a feasible option when normal blastocysts are unavailable. -
近年来,我国的不孕症比例为12.5%[1],人类辅助生殖技术(assisted reproductive technology,ART)已成为治疗不孕症的重要方法[2]。正常受精是指受精后16~20 h内观察到受精卵中有2个清晰的原核(2 pronucleus, 2PN)和2个极体(2 polar body,2PB)[3]。无原核(0 pronucleus, 0PN)、1个原核(1 pronucleus, 1PN)、3个或更多原核(3 pronucleus, 3PN)的受精卵被认为受精异常,通常被丢弃[4]。然而,有研究[5]表明,0PN或1PN受精卵发育形成的囊胚可以获得正常的活产。目前,0PN受精卵卵裂形成胚胎(0PN衍生胚胎)的发生尚不清楚,其移植适用性也存在争议。针对这些问题,本研究旨在调查本院生殖中心收治的0PN衍生胚胎患者的实验室数据,以期为临床提供一定的指导。
1. 资料与方法
1.1 临床资料
对2019年9月—2022年5月期间在安徽医科大学第一附属医院生殖医学中心接受ART治疗且至少有一个囊胚移植周期夫妇的临床数据进行回顾性分析。2PN+0PN组每个周期中至少有一个0PN衍生胚胎,2PN组每个周期中全为2PN受精卵卵裂形成胚胎(2PN衍生胚胎)。1PN、≥3PN受精胚胎的周期被排除在样本群体之外。共9 167个周期,首先分为2PN+0PN组6 915个周期和2PN组2 252个周期;再根据0PN衍生胚胎的比例将体外受精(in vitro fertilization, IVF)周期中患者进一步分为L组(0~30%, 2 579例)、M组(31%~60%, 782例)和H组(61%~100%, 221例);最后从L组中选取只含2PN衍生胚胎的100例周期(2PN100%组),在H组中选取只含0PN衍生胚胎的72例周期(0PN100%组)。本研究经安徽医科大学伦理委员会批准(20200114)。
1.2 治疗方法
1.2.1 实验室方案
在IVF后18~20 h或卵胞浆内单精子注射(intracytoplasmic sperm injection, ICSI)后16~18 h进行受精评估,含有2个原核与2个极体,并表现出正常形态被评估为2PN,无原核被评估为0PN,有1个原核被评估为1PN,有3个原核被评估为3PN。在第3天观察卵裂球的数量以及碎片程度,具有7~9个卵裂球且碎片率低于20%的胚胎为优质胚胎。将胚胎转移到囊胚培养基中进一步培养2~3 d,在第5天和第6天使用Gardner囊胚分级方法评估囊胚[6]。内细胞团按照细胞数目的多少以及排列情况分为3个等级:A级,细胞数目多,排列紧密;B级,细胞数目少,排列松散;C级,细胞数目很少。滋养层同样是按照细胞的数目以及结构情况分为3个等级:A级,上皮细胞层由较多的细胞组成,结构紧密;B级,上皮细胞层由不多的细胞组成,结构松散;C级,上皮细胞由稀疏的细胞组成。优质囊胚被定义为第5天得分≥3BB,第6天得分为≥4BB。最后,将获得的囊胚通过玻璃化冷冻,随后储存在-196 ℃的液氮中。
1.2.2 胚胎移植和随访
在超声引导下将1~2个囊胚植入子宫。在无2PN受精卵来源的囊胚可供移植的情况下,结合患者的意见及临床实践经验来选择最优质的0PN受精卵来源的囊胚进行移植。生化妊娠定义为胚胎移植后14 d左右血液中β-人绒毛膜促性腺激素(β-human chorionic gonadotrophin,β-hCG)值超过正常值2次,但无临床妊娠。临床妊娠定义为胚胎移植4~7周后B超介导下子宫内可见孕囊组织或流产物病理证实[7]。
1.3 统计学方法
采用GraphPad Prism 8.0和SPSS 23.0统计学软件进行统计分析。符合正态分布的计量资料用x±s表示,2组间比较采用成组t检验,多组间比较采用方差分析;偏态分布的计量资料用M(P25, P75)表示,2组或多组间比较采用Mann-Whitney U检验;计数资料以百分率表示,组间比较采用χ2检验;采用多因素logistic回归分析研究0PN衍生胚胎发生的影响因素。P<0.05为差异有统计学意义。
2. 结果
2.1 2PN+0PN组和2PN组患者基础临床资料分析
2PN+0PN组和2PN组患者BMI差异无统计学意义,而2组促卵泡生成素(follicle-stimulating hormone,FSH)、促黄体生成素(luteinizing hormone,LH)、使用促性腺激素(gonadotropin,Gn)时间、Gn剂量、女方年龄,以及女方原发性不孕症、多囊卵巢综合征(polycystic ovary syndrome,PCOS)和子宫内膜异位症的发生率差异均有统计学意义(P<0.05),见表 1。以是否含有0PN衍生胚胎为因变量(是=1,否=0),FSH、LH、Gn时间、Gn剂量(IU)、女方年龄(岁)、合并原发不孕、合并PCOS、合并子宫内膜异位症为自变量,行多因素logistic回归分析,进一步证实这些因素均为0PN衍生胚胎发生的影响因素(P<0.05),见表 2。
表 1 2PN+0PN组和2PN组接受ART治疗患者的基本临床资料比较Table 1. Comparison of basic clinical data of patients treated with ART between 2PN+0PN group and 2PN group项目 2PN+0PN组 2PN组 统计量 P值 总周期数(个) 6 915 2 252 BMI(x±s) 22.33±8.50 22.15±3.23 1.233a 0.327 FSH[M(P25, P75), IU/L] 7.24 (6.00, 8.73) 7.76 (6.46, 9.66) -10.080b <0.001 LH[M(P25, P75), IU/L] 4.670(3.310,6.590) 4.390(3.173,5.960) 5.391b <0.001 Gn时间(x±s,d) 10.64±2.07 10.25±2.47 7.037a <0.001 Gn剂量[M(P25, P75), IU/L] 2 075.00 (1 650.00,2 700.00) 2 250.00(1 737.500,2 875.00) -4.989b <0.001 女方年龄[M(P25, P75), 岁] 31 (28, 34) 32 (29, 37) -9.243b <0.001 原发不孕比例(%) 52.10(3 603/6 915) 49.33(1 111/2 252) 5.219c 0.022 PCOS比例(%) 17.05(1 179/6 915) 7.37(166/2 252) 127.100c <0.001 子宫内膜异位症比例(%) 2.86(198/6 915) 4.09(92/2 252) 8.280c 0.004 注:a为t值,b为Z值, c为χ2值。 表 2 0PN衍生胚胎发生相关因素的多因素logistic回归分析Table 2. Multivariate Logistic regression analysis of factors associated with 0PN embryogenesis变量 B SE Waldχ2 P值 OR(95% CI) FSH -0.149 0.010 237.428 <0.001 0.861(0.845~0.878) LH 0.036 0.009 16.765 <0.001 1.036(1.019~1.054) Gn时间 0.068 0.016 18.931 <0.001 1.070(1.038~1.103) Gn剂量 0.000 0.000 16.881 <0.001 1.000(1.000~1.000) 女方年龄 -0.036 0.009 15.803 <0.001 0.964(0.947~0.982) 合并原发不孕 -0.335 0.089 14.193 0.002 0.715(0.601~0.851) 合并PCOS 1.884 0.142 175.570 <0.001 6.580(4.979~8.694) 合并子宫内膜异位症 0.538 0.205 6.912 0.009 1.713(1.147~2.559) 注:变量赋值如下,FSH、LH、Gn时间、Gn剂量、女方年龄均以实际值赋值;合并原发不孕,是=1,否=0;合并PCOS,是=1,否=0;合并子宫内膜异位症,是=1,否=0。 2.2 2PN+0PN组和2PN组胚胎发育和临床结局比较
2PN+0PN组的获卵数、总受精率显著高于2PN组,2组总卵裂率相近。2PN组的优质胚胎率、囊胚形成率、优质囊胚率均显著高于2PN+0PN组。然而,与2PN组比较,2PN+0PN组的累计临床妊娠率(cumulative clinical pregnancy rate, CCR)和累计活产率(cumulative live birth rate, CLR)更高。2组流产率、新生儿体重、Apgar评分比较差异均无统计学意义(P>0.05), 见表 3。
表 3 2PN+0PN组和2PN组接受ART治疗患者胚胎发育和临床结局比较Table 3. Comparison of embryonic development and clinical outcomes in patients receiving ART between the 2PN+0PN group and the 2PN group项目 2PN+0PN组 2PN组 统计量 P值 总周期数(个) 6 915 2 252 获卵数[M(P25, P75),个] 12.0(7.0,18.0) 8.5 (5.0, 14.0) -8.761a <0.001 2PN受精数(个) 55 960 12 140 0PN受精数(个) 23 023 0 总受精率(2PN+0PN,%) 72.32(78 983/109 212) 63.52(12 140/19 111) 611.500b <0.001 总卵裂率(2PN+0PN,%) 97.86(77 289/78 983) 98.01(11 899/12 140) 1.289b 0.256 2PN卵裂率(%) 96.97(54 266/55 960) 100.00(11 899/11 899) 369.400b <0.001 0PN卵裂率(%) 100.00(23 023/23 023) 优质胚胎率(%) 43.57(33 676/77 289) 47.98(5 709/11 899) 81.230b <0.001 囊胚形成率(%) 55.01(42 518/77 289) 62.44(7 430/11 899) 231.100b <0.001 优质囊胚率(%) 44.51(34 400/77 289) 48.15(5 729/11 899) 55.160b <0.001 累计临床妊娠率(%) 79.68(5 510/6 915) 64.08(1 443/2 252) 225.800b <0.001 累计活产率(%) 64.99(4 494/6 915) 54.97(1 238/2 252) 72.730b <0.001 流产率(%) 9.38(517/5 510) 9.36(135/1 443) 0.001b 0.975 新生儿体重(x±s,g) 3 231.0±651.1 3 196.0±658.4 1.642c 0.101 Apgar评分(x±s,分) 9.95±0.33 9.93±0.37 1.858c 0.063 注:a为Z值,b为χ2值,c为t值。2PN受精数、0PN受精数反应总受精数的一部分,未进行比较。 2.3 IVF周期中不同0PN衍生胚胎比例的胚胎发育及临床结果
L、M和H组的获卵数与受精率呈递减趋势。M组的卵裂率显著高于其余2组,优质胚胎率、优质囊胚率显著高于L组。M组与H组的囊胚形成率显著高于L组。CCR和CLR依次递减。此外,L组的流产率显著高于M组,见表 4。
表 4 IVF周期中不同0PN衍生胚胎比例的胚胎发育及临床结果比较Table 4. Comparison of embryo development and clinical outcomes of different 0PN embryo proportions in IVF cycles项目 L组 M组 H组 统计量 P值 总周期数(个) 2 579 782 221 获卵数[M(P25, P75),个] 15(10, 21) 10(5,16)a 4(2, 9)ab 327.800c <0.001 受精率(%) 79.25(34 715/43 806) 77.72(7 957/10 238)a 76.16(1 444/1 896)a 20.206d <0.001 卵裂率(%) 97.79(33 947/34 715) 98.74(7 857/7 957)a 97.09(1 402/1 444)b 34.544d <0.001 优质胚胎率(%) 43.46(14 754/33 947) 46.47(3 651/7 857)a 43.94(616/1 402) 23.404d <0.001 囊胚形成率(%) 53.70(18 231/33 947) 57.46(4 515/7 857)a 56.56(793/1 402)a 38.911d <0.001 优质囊胚率(%) 44.33(15 049/33 947) 47.36(3 721/7 857)a 45.01(631/1 402) 23.654d <0.001 累计临床妊娠率(%) 85.07(2 194/2 579) 78.26(612/782)a 66.06(146/221)ab 62.636d <0.001 累计活产率(%) 70.61(1 821/2 579) 66.75(522/782)a 55.20(122/221)ab 24.498d <0.001 流产率(%) 8.34(183/2 194) 5.39(33/612)a 8.22(12/146) 6.373d 0.041 新生儿体重(x±s,g) 3 223.0±625.0 3 190.0±654.4 3 365.0±680.5ab 4.872e 0.088 Apgar评分(x±s,分) 9.95±0.35 9.95±0.36 9.92±0.51 0.839e 0.432 注:与L组比较,aP<0.05;与M组比较,bP<0.05。c为Z值,d为χ2值,e为F值。 2.4 0PN100%组与2PN100%组周期胚胎发育及临床结局比较
在2组间基本临床指标无差异的情况下,0PN100%组的获卵数显著少于2PN100%组(P<0.001),2PN100%组的优质胚胎率、优质囊胚率、CCR和CLR显著高于0PN100%组(P<0.05),见表 5。
表 5 0PN100%组与2PN100%组周期基本临床资料、胚胎发育及临床结局比较Table 5. Comparison of basic clinical data, embryo development, and clinical outcome between the 0PN100% group and the 2PN100% group项目 0PN100%组 2PN100%组 统计量 P值 总周期数(个) 72 100 FSH[M(P25, P75),个] 8.950(6.640, 11.230) 9.065(7.158, 11.762) -0.711a 0.477 LH[M(P25, P75),个] 4.400(2.990, 6.920) 4.710(3.380, 7.100) -0.843a 0.399 Gn时间(x±s,d) 9.77±3.09 10.16±2.12 0.806b 0.422 Gn剂量[M(P25, P75),IU] 2 287.50(1 743.75, 3 337.50) 2 250.00(1 725.00, 3 225.00) 0.142a 0.887 女方年龄(x±s,岁) 33.56±6.48 33.21±6.27 0.329b 0.743 原发不孕比例(%) 43.06(31/72) 45.00(45/100) 0.064c 0.800 PCOS比例(%) 6.94(5/72) 8.00(8/100) 0.067c 0.796 子宫内膜异位症比例(%) 1.39(1/72) 5.00(5/100) 1.621c 0.203 获卵数[M(P25, P75),个] 2(1,5) 11(8,13) -8.891a <0.001 受精率(%) 64.23(167/260) 64.62(579/896) 0.013c 0.908 卵裂率(%) 100.00(167/167) 98.96(573/579) 1.745c 0.187 优质胚胎率(%) 30.54(51/167) 53.40(306/573) 27.070c <0.001 囊胚形成率(%) 55.09(92/167) 62.83(360/573) 3.257c 0.196 优质囊胚率(%) 32.34(54/167) 53.05(304/573) 22.230c <0.001 累计临床妊娠率(%) 40.28(29/72) 67.00(67/100) 12.120c 0.001 累计活产率(%) 30.56(22/72) 60.00(60/100) 14.550c <0.001 流产率(%) 3.45(1/29) 11.94(8/67) 1.718c 0.424 新生儿体重(x±s,g) 3 137.0±643.5 3 101.0±538.0 0.993b 0.321 Apgar评分(x±s,分) 10.00±0.00 10.00±0.06 1.416b 0.157 注:a为Z值,b为t值,c为χ2值。 3. 讨论
在受精评估后0PN受精卵有时被一些生殖中心直接丢弃[8]。但其中一些胚胎具有进一步发育成高质量囊胚的能力。在无2PN来源的囊胚可用于移植的情况下,成功利用0PN来源的囊胚可以显著提高卵母细胞的利用率。
本研究结果表明,L、M、H组的CCR与CLR依次递减,证实了0PN受精卵的比例过高, 2PN受精卵占比过低,不利于患者后续的临床结果。而L组的流产率显著高于M组(8.34% vs. 5.39%,P<0.05)。有研究[9]表明,有11.3%~20.0%的成熟卵母细胞在显微镜下呈现0PN现象,L组在纳入数据时总获卵数高于M组,这使得L组周期内含有0PN受精卵的个数高于M组,李澎涛等[10]发现,0PN来源囊胚比2PN来源囊胚冻融移植的流产率(40.0% vs. 20.8%)更高。然而,L组的囊胚形成率却显著低于M组(53.70% vs. 57.46%,P<0.001)与H组(53.70% vs. 56.56%,P<0.05),这可能是由于M、H组中许多最初被识别为0PN的受精卵可能并不真正缺乏发育潜力。原核最早可在受精后5 h被观察到[11]。在受精检查时最初被鉴定为缺乏原核的受精卵实际上可能是具有2PN的受精卵,但原核可能在检查前消失或在检查后出现[12],在临床实践中确定0PN受精卵时需要谨慎。推荐应用延时培养系统(time-lapse system, TLS)作为减少0PN受精卵发生率的潜在解决方案[13]。
近20年来,围绕0PN衍生胚胎移植的争议主要是这些胚胎是否面临染色体异常的风险[14]。荧光原位杂交技术分析[15]发现,只有3%和5%的0PN和1PN衍生胚胎显示单倍体核型,石小丹等[16]通过植入前遗传学检测技术(PGT)对78枚0PN来源囊胚检测,发现整倍体率仅为28.21%,显著低于2PN来源囊胚的46.53%(P<0.05)。这些发现显示0PN衍生胚胎可能具有与2PN衍生胚胎相似的染色体组成,表明它们具有临床移植的潜力[17-18]。
综上所述,本研究发现,尽管与0PN受精卵相比,2PN受精卵具有更高的发育潜力和更好的妊娠结局,但值得注意的是,0PN衍生囊胚的移植对新生儿体重或Apgar评分未发现不利影响。因此,对于某些缺乏正常受精的患者,将0PN衍生胚胎进行囊胚移植能为患者提供额外的怀孕机会。
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表 1 2PN+0PN组和2PN组接受ART治疗患者的基本临床资料比较
Table 1. Comparison of basic clinical data of patients treated with ART between 2PN+0PN group and 2PN group
项目 2PN+0PN组 2PN组 统计量 P值 总周期数(个) 6 915 2 252 BMI(x±s) 22.33±8.50 22.15±3.23 1.233a 0.327 FSH[M(P25, P75), IU/L] 7.24 (6.00, 8.73) 7.76 (6.46, 9.66) -10.080b <0.001 LH[M(P25, P75), IU/L] 4.670(3.310,6.590) 4.390(3.173,5.960) 5.391b <0.001 Gn时间(x±s,d) 10.64±2.07 10.25±2.47 7.037a <0.001 Gn剂量[M(P25, P75), IU/L] 2 075.00 (1 650.00,2 700.00) 2 250.00(1 737.500,2 875.00) -4.989b <0.001 女方年龄[M(P25, P75), 岁] 31 (28, 34) 32 (29, 37) -9.243b <0.001 原发不孕比例(%) 52.10(3 603/6 915) 49.33(1 111/2 252) 5.219c 0.022 PCOS比例(%) 17.05(1 179/6 915) 7.37(166/2 252) 127.100c <0.001 子宫内膜异位症比例(%) 2.86(198/6 915) 4.09(92/2 252) 8.280c 0.004 注:a为t值,b为Z值, c为χ2值。 表 2 0PN衍生胚胎发生相关因素的多因素logistic回归分析
Table 2. Multivariate Logistic regression analysis of factors associated with 0PN embryogenesis
变量 B SE Waldχ2 P值 OR(95% CI) FSH -0.149 0.010 237.428 <0.001 0.861(0.845~0.878) LH 0.036 0.009 16.765 <0.001 1.036(1.019~1.054) Gn时间 0.068 0.016 18.931 <0.001 1.070(1.038~1.103) Gn剂量 0.000 0.000 16.881 <0.001 1.000(1.000~1.000) 女方年龄 -0.036 0.009 15.803 <0.001 0.964(0.947~0.982) 合并原发不孕 -0.335 0.089 14.193 0.002 0.715(0.601~0.851) 合并PCOS 1.884 0.142 175.570 <0.001 6.580(4.979~8.694) 合并子宫内膜异位症 0.538 0.205 6.912 0.009 1.713(1.147~2.559) 注:变量赋值如下,FSH、LH、Gn时间、Gn剂量、女方年龄均以实际值赋值;合并原发不孕,是=1,否=0;合并PCOS,是=1,否=0;合并子宫内膜异位症,是=1,否=0。 表 3 2PN+0PN组和2PN组接受ART治疗患者胚胎发育和临床结局比较
Table 3. Comparison of embryonic development and clinical outcomes in patients receiving ART between the 2PN+0PN group and the 2PN group
项目 2PN+0PN组 2PN组 统计量 P值 总周期数(个) 6 915 2 252 获卵数[M(P25, P75),个] 12.0(7.0,18.0) 8.5 (5.0, 14.0) -8.761a <0.001 2PN受精数(个) 55 960 12 140 0PN受精数(个) 23 023 0 总受精率(2PN+0PN,%) 72.32(78 983/109 212) 63.52(12 140/19 111) 611.500b <0.001 总卵裂率(2PN+0PN,%) 97.86(77 289/78 983) 98.01(11 899/12 140) 1.289b 0.256 2PN卵裂率(%) 96.97(54 266/55 960) 100.00(11 899/11 899) 369.400b <0.001 0PN卵裂率(%) 100.00(23 023/23 023) 优质胚胎率(%) 43.57(33 676/77 289) 47.98(5 709/11 899) 81.230b <0.001 囊胚形成率(%) 55.01(42 518/77 289) 62.44(7 430/11 899) 231.100b <0.001 优质囊胚率(%) 44.51(34 400/77 289) 48.15(5 729/11 899) 55.160b <0.001 累计临床妊娠率(%) 79.68(5 510/6 915) 64.08(1 443/2 252) 225.800b <0.001 累计活产率(%) 64.99(4 494/6 915) 54.97(1 238/2 252) 72.730b <0.001 流产率(%) 9.38(517/5 510) 9.36(135/1 443) 0.001b 0.975 新生儿体重(x±s,g) 3 231.0±651.1 3 196.0±658.4 1.642c 0.101 Apgar评分(x±s,分) 9.95±0.33 9.93±0.37 1.858c 0.063 注:a为Z值,b为χ2值,c为t值。2PN受精数、0PN受精数反应总受精数的一部分,未进行比较。 表 4 IVF周期中不同0PN衍生胚胎比例的胚胎发育及临床结果比较
Table 4. Comparison of embryo development and clinical outcomes of different 0PN embryo proportions in IVF cycles
项目 L组 M组 H组 统计量 P值 总周期数(个) 2 579 782 221 获卵数[M(P25, P75),个] 15(10, 21) 10(5,16)a 4(2, 9)ab 327.800c <0.001 受精率(%) 79.25(34 715/43 806) 77.72(7 957/10 238)a 76.16(1 444/1 896)a 20.206d <0.001 卵裂率(%) 97.79(33 947/34 715) 98.74(7 857/7 957)a 97.09(1 402/1 444)b 34.544d <0.001 优质胚胎率(%) 43.46(14 754/33 947) 46.47(3 651/7 857)a 43.94(616/1 402) 23.404d <0.001 囊胚形成率(%) 53.70(18 231/33 947) 57.46(4 515/7 857)a 56.56(793/1 402)a 38.911d <0.001 优质囊胚率(%) 44.33(15 049/33 947) 47.36(3 721/7 857)a 45.01(631/1 402) 23.654d <0.001 累计临床妊娠率(%) 85.07(2 194/2 579) 78.26(612/782)a 66.06(146/221)ab 62.636d <0.001 累计活产率(%) 70.61(1 821/2 579) 66.75(522/782)a 55.20(122/221)ab 24.498d <0.001 流产率(%) 8.34(183/2 194) 5.39(33/612)a 8.22(12/146) 6.373d 0.041 新生儿体重(x±s,g) 3 223.0±625.0 3 190.0±654.4 3 365.0±680.5ab 4.872e 0.088 Apgar评分(x±s,分) 9.95±0.35 9.95±0.36 9.92±0.51 0.839e 0.432 注:与L组比较,aP<0.05;与M组比较,bP<0.05。c为Z值,d为χ2值,e为F值。 表 5 0PN100%组与2PN100%组周期基本临床资料、胚胎发育及临床结局比较
Table 5. Comparison of basic clinical data, embryo development, and clinical outcome between the 0PN100% group and the 2PN100% group
项目 0PN100%组 2PN100%组 统计量 P值 总周期数(个) 72 100 FSH[M(P25, P75),个] 8.950(6.640, 11.230) 9.065(7.158, 11.762) -0.711a 0.477 LH[M(P25, P75),个] 4.400(2.990, 6.920) 4.710(3.380, 7.100) -0.843a 0.399 Gn时间(x±s,d) 9.77±3.09 10.16±2.12 0.806b 0.422 Gn剂量[M(P25, P75),IU] 2 287.50(1 743.75, 3 337.50) 2 250.00(1 725.00, 3 225.00) 0.142a 0.887 女方年龄(x±s,岁) 33.56±6.48 33.21±6.27 0.329b 0.743 原发不孕比例(%) 43.06(31/72) 45.00(45/100) 0.064c 0.800 PCOS比例(%) 6.94(5/72) 8.00(8/100) 0.067c 0.796 子宫内膜异位症比例(%) 1.39(1/72) 5.00(5/100) 1.621c 0.203 获卵数[M(P25, P75),个] 2(1,5) 11(8,13) -8.891a <0.001 受精率(%) 64.23(167/260) 64.62(579/896) 0.013c 0.908 卵裂率(%) 100.00(167/167) 98.96(573/579) 1.745c 0.187 优质胚胎率(%) 30.54(51/167) 53.40(306/573) 27.070c <0.001 囊胚形成率(%) 55.09(92/167) 62.83(360/573) 3.257c 0.196 优质囊胚率(%) 32.34(54/167) 53.05(304/573) 22.230c <0.001 累计临床妊娠率(%) 40.28(29/72) 67.00(67/100) 12.120c 0.001 累计活产率(%) 30.56(22/72) 60.00(60/100) 14.550c <0.001 流产率(%) 3.45(1/29) 11.94(8/67) 1.718c 0.424 新生儿体重(x±s,g) 3 137.0±643.5 3 101.0±538.0 0.993b 0.321 Apgar评分(x±s,分) 10.00±0.00 10.00±0.06 1.416b 0.157 注:a为Z值,b为t值,c为χ2值。 -
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