囊胚期与卵裂期新鲜胚胎移植单胎分娩新生儿结局的Meta分析

doi:10.12280/gjszjk.20200741

摘要/Abstract

摘要：

目的: 系统评价新鲜取卵周期中囊胚期和卵裂期胚胎移植后单胎分娩的新生儿结局。方法: 系统检索PubMed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库（CBM）、中国知网全文数据库（CNKI）、万方和维普数据库（截至2020年11月）,查找关于囊胚期和卵裂期新鲜胚胎移植后单胎分娩新生儿结局的相关研究。评价者按照纳入标准和排除标准对文献进行筛选、质量评价和数据提取,采用RevMan 5.3软件进行数据分析。结果: 共纳入符合要求的研究13篇。总体分析结果显示,与卵裂期胚胎移植相比,囊胚期胚胎移植后极早产儿（VPTB,RR=1.17,95%CI：1.08~1.26,P<0.000 1）和大于胎龄儿（LGA,RR=1.11,95%CI：1.04~1.19,P=0.002）发生率显著增高,小于胎龄儿（SGA,RR=0.85,95%CI：0.78~0.93,P=0.000 6）发生率显著降低,而早产儿（PTB,RR=1.10,95%CI：0.98~1.22,P=0.09）、低出生体质量儿（LBW,RR=1.00, 95%CI：0.94~1.07,P=0.90）和极低出生体质量儿（VLBW,RR=0.99,95%CI：0.89~1.10,P=0.88）差异无统计学意义。亚组分析结果显示,北美洲囊胚组新生儿PTB发生率显著高于卵裂期胚胎组（RR=1.28,95%CI：1.23~1.33,P<0.000 01）。结论: 在新鲜移植周期单胎出生的新生儿中,与卵裂期胚胎移植相比,囊胚移植后VPTB、LGA的风险增高,SGA的风险降低。

关键词: 分裂期,卵, 囊胚, 胚胎移植, 新生儿结局, Meta分析

Abstract:

Objective: To evaluate systematically the neonatal outcomes of single delivery after embryo transfer at blastocyst and cleavage stages in the fresh cycles. Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, CBM, CNKI, Wanfang and VIP databases (up to November 2020) to search the related studies on the neonatal outcomes of single birth after blastocyst and cleavage stage fresh embryo transfer. The evaluators screened the literature, evaluated the quality and extracted the data according to the inclusion and exclusion criteria. The RevMan 5.3 software was used for data analysis. Results: Thirteen studies were scrutinized for this meta-analysis. The overall showed that the incidences of very preterm birth (VPTB, RR=1.17, 95%CI: 1.08-1.26, P<0.000 1) and large for gestational age (LGA, RR=1.11, 95%CI: 1.04-1.19, P=0.002) were significantly increased, and the incidence of small for gestational age (SGA, RR=0.85, 95%CI: 0.78-0.93, P=0.000 6) was significantly decreased, in the single delivery after the blastocyst embryo transfer when compared with the embryo transfer at cleavage stage. There were no significant differences in the incidences of preterm birth (PTB, RR=1.10, 95%CI: 0.98-1.22, P=0.09), low birth weight (LBW, RR=1.00, 95%CI: 0.94-1.07, P=0.90) and very low birth weight (VLBW, RR=0.99, 95%CI: 0.89-1.10, P=0.88). Subgroup analysis showed that the incidence of neonatal PTB in the blastocyst group was significantly higher than that in the cleavage-embryo group (RR=1.28, 95%CI: 1.23-1.33, P<0.000 01). Conclusions: In the neonatal outcomes of single delivery in the fresh cycles, blastocyst transfer has the higher risks of VPTB and LGA and lower risk of SGA when compared with cleavage embryo transfer.

Key words: Cleavage stage, ovum, Blastula, Embryo transfer, Neonatal outcomes, Meta-analysis

张卉, 柴亮听, 卢静, 王常燕, 常文亮. 囊胚期与卵裂期新鲜胚胎移植单胎分娩新生儿结局的Meta分析[J]. 国际生殖健康/计划生育, 2021, 40(5): 359-365.

ZHANG Hui, CHAI Liang-ting, LU Jing, WANG Chang-yan, CHANG Wen-liang. Neonatal Outcomes of Single Delivery after Embryo Transfer at Blastocyst and Cleavage Stages in Fresh Cycles: A Meta-Analysis[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(5): 359-365.

图/表 9

参考文献 28

[1]	Gorodeckaja J, Neumann S, McCollin A, et al. High implantation and clinical pregnancy rates with single vitrified-warmed blastocyst transfer and optional aneuploidy testing for all patients[J]. Hum Fertil (Camb), 2020, 23(4):256-267. doi: 10.1080/14647273.2018.1551628. doi: 10.1080/14647273.2018.1551628 URL
[2]	Tran D, Cooke S, Illingworth PJ, et al. Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer[J]. Hum Reprod, 2019, 34(6):1011-1018. doi: 10.1093/humrep/dez064. doi: 10.1093/humrep/dez064
[3]	Evans J, Rai A, Nguyen H, et al. Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal-Embryo Communication[J]. Proteomics, 2019, 19(23):e1800423. doi: 10.1002/pmic.201800423. doi: 10.1002/pmic.201800423
[4]	Glujovsky D, Farquhar C, Quinteiro Retamar AM, et al. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology[J]. Cochrane Database Syst Rev, 2016(6):CD002118. doi: 10.1002/14651858.CD002118.pub5. doi: 10.1002/14651858.CD002118.pub5
[5]	Vega M, Zaghi S, Buyuk E, et al. Not all twins are monozygotic after elective single embryo transfer: analysis of 32,600 elective single embryo transfer cycles as reported to the Society for Assisted Reproductive Technology[J]. Fertil Steril, 2018, 109(1):118-122. doi: 10.1016/j.fertnstert.2017.10.003. doi: 10.1016/j.fertnstert.2017.10.003 URL
[6]	Wang X, Du M, Guan Y, et al. Comparative neonatal outcomes in singleton births from blastocyst transfers or cleavage-stage embryo transfers: a systematic review and meta-analysis[J]. Reprod Biol Endocrinol, 2017, 15(1):36. doi: 10.1186/s12958-017-0255-4. doi: 10.1186/s12958-017-0255-4 URL
[7]	Alviggi C, Conforti A, Carbone IF, et al. Influence of cryopreservation on perinatal outcome after blastocyst-vs cleavage-stage embryo transfer: systematic review and meta-analysis[J]. Ultrasound Obstet Gynecol, 2018, 51(1):54-63. doi: 10.1002/uog.18942. doi: 10.1002/uog.18942 pmid: 29077229
[8]	Litzky JF, Boulet SL, Esfandiari N, et al. Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry study[J]. J Assist Reprod Genet, 2018, 35(6):1027-1037. doi: 10.1007/s10815-018-1168-7. doi: 10.1007/s10815-018-1168-7 URL
[9]	Shi W, Zhang W, Li N, et al. Comparison of perinatal outcomes following blastocyst and cleavage-stage embryo transfer: analysis of 10 years′ data from a single centre[J]. Reprod Biomed Online, 2019, 38(6):967-978. doi: 10.1016/j.rbmo.2018.12.031. doi: 10.1016/j.rbmo.2018.12.031 URL
[10]	Marconi N, Raja EA, Bhattacharya S, et al. Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: a retrospective analysis of 67 147 IVF/ICSI cycles[J]. Hum Reprod, 2019, 34(9):1716-1725. doi: 10.1093/humrep/dez133. doi: 10.1093/humrep/dez133
[11]	Dar S, Librach CL, Gunby J, et al. Increased risk of preterm birth in singleton pregnancies after blastocyst versus Day 3 embryo transfer: Canadian ART Register (CARTR) analysis[J]. Hum Reprod, 2013, 28(4):924-928. doi: 10.1093/humrep/des448. doi: 10.1093/humrep/des448 URL
[12]	De Vos A, Janssens R, Van de Velde H, et al. The type of culture medium and the duration of in vitro culture do not influence birthweight of ART singletons[J]. Hum Reprod, 2015, 30(1):20-27. doi: 10.1093/humrep/deu286. doi: 10.1093/humrep/deu286 URL
[13]	De Vos A, Santos-Ribeiro S, Van Landuyt L, et al. Birthweight of singletons born after cleavage-stage or blastocyst transfer in fresh and warming cycles[J]. Hum Reprod, 2018, 33(2):196-201. doi: 10.1093/humrep/dex361. doi: 10.1093/humrep/dex361 URL
[14]	Ishihara O, Araki R, Kuwahara A, et al. Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan[J]. Fertil Steril, 2014, 101(1):128-133. doi: 10.1016/j.fertnstert.2013.09.025. doi: 10.1016/j.fertnstert.2013.09.025 pmid: 24268706
[15]	Kalra SK, Ratcliffe SJ, Barnhart KT, et al. Extended embryo culture and an increased risk of preterm delivery[J]. Obstet Gynecol, 2012, 120(1):69-75. doi: 10.1097/AOG.0b013e31825b88fc. doi: 10.1097/AOG.0b013e31825b88fc URL
[16]	Marconi N, Raja EA, Bhattacharya S, et al. Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: a retrospective analysis of 67 147 IVF/ICSI cycles[J]. Hum Reprod, 2019, 34(9):1716-1725. doi: 10.1093/humrep/dez133. doi: 10.1093/humrep/dez133
[17]	Maxwell SM, Melzer-Ross K, McCulloh DH, et al. A comparison of pregnancy outcomes between day 3 and day 5/6 embryo transfers: does day of embryo transfer really make a difference?[J]. J Assist Reprod Genet, 2015, 32(2):249-254. doi: 10.1007/s10815-014-0404-z. doi: 10.1007/s10815-014-0404-z URL
[18]	Oron G, Sokal-Arnon T, Son WY, et al. Extended embryo culture is not associated with increased adverse obstetric or perinatal outcome[J]. Am J Obstet Gynecol, 2014, 211(2):165.e1-e7. doi: 10.1016/j.ajog.2014.03.018. doi: 10.1016/j.ajog.2014.03.018
[19]	Pereira N, Pryor KP, Petrini AC, et al. Perinatal Risks Associated with Early Vanishing Twin Syndrome following Transfer of Cleavage- or Blastocyst-Stage Embryos[J]. J Pregnancy, 2016, 2016:1245210. doi: 10.1155/2016/1245210. doi: 10.1155/2016/1245210 pmid: 28101380
[20]	Shi W, Zhang W, Li N, et al. Comparison of perinatal outcomes following blastocyst and cleavage-stage embryo transfer: analysis of 10 years′ data from a single centre[J]. Reprod Biomed Online, 2019, 38(6):967-978. doi: 10.1016/j.rbmo.2018.12.031. doi: 10.1016/j.rbmo.2018.12.031 URL
[21]	Spangmose AL, Ginström Ernstad E, Malchau S, et al. Obstetric and perinatal risks in 4601 singletons and 884 twins conceived after fresh blastocyst transfers: a Nordic study from the CoNARTaS group[J]. Hum Reprod, 2020, 35(4):805-815. doi: 10.1093/humrep/deaa032. doi: 10.1093/humrep/deaa032 URL
[22]	Zhu J, Lin S, Li M, et al. Effect of in vitro culture period on birthweight of singleton newborns[J]. Hum Reprod, 2014, 29(3):448-454. doi: 10.1093/humrep/det460. doi: 10.1093/humrep/det460 URL
[23]	刘文霞, 杜明泽, 刘曼曼, 等. 新鲜周期卵裂胚和囊胚移植单胎分娩的新生儿结局及影响因素[J]. 新乡医学院学报, 2019, 36(9):868-871. doi: 10.7683/xxyxyxb.2019.09.015. doi: 10.7683/xxyxyxb.2019.09.015
[24]	Tiitinen A. Single embryo transfer: Why and how to identify the embryo with the best developmental potential[J]. Best Pract Res Clin Endocrinol Metab, 2019, 33(1):77-88. doi: 10.1016/j.beem.2019.04.001. doi: S1521-690X(19)30010-7 pmid: 31005505
[25]	De Croo I, De Sutter P, Tilleman K. A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic[J]. Hum Reprod Open, 2020, 2020(3):hoaa034. doi: 10.1093/hropen/hoaa034. doi: 10.1093/hropen/hoaa034 URL
[26]	De Vos A, Van Landuyt L, Santos-Ribeiro S, et al. Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle[J]. Hum Reprod, 2016, 31(11):2442-2449. doi: 10.1093/humrep/dew219. doi: 10.1093/humrep/dew219 URL
[27]	Glujovsky D, Farquhar C. Cleavage-stage or blastocyst transfer: what are the benefits and harms?[J]. Fertil Steril, 2016, 106(2):244-250. doi: 10.1016/j.fertnstert.2016.06.029. doi: 10.1016/j.fertnstert.2016.06.029 pmid: 27421614
[28]	Wang S, Chen L, Fang J, et al. Comparison of the pregnancy and obstetric outcomes between single cleavage-stage embryo transfer and single blastocyst transfer by time-lapse selection of embryos[J]. Gynecol Endocrinol, 2019, 35(9):792-795. doi: 10.1080/09513590.2019.1594762. doi: 10.1080/09513590.2019.1594762 URL

研究文献	国家	统计时间	数据来源	研究类型	受精方式	移植时间	结局指标	NOS评分
Dar 2013^[11]	加拿大	2001—2009	多中心	队列研究	IVF/ICSI	day3 vs. day5/6	①~④	9
De Vos 2015^[12]	比利时	2004.04—2009.12	单中心	队列研究	IVF/ICSI	day3 vs. day5	①~④	8
De Vos 2018^[13]	比利时	2010.09—2015.08	单中心	队列研究	IVF/ICSI	day 3 vs. day 5	①~④	8
Ishihara 2014^[14]	日本	2008—2010	多中心	队列研究	IVF/ICSI	未提及	①~⑥	8
Kalra 2012^[15]	美国	2004—2006	多中心	队列研究	IVF	day 3 vs. day5/6	①~③	8
Marconi 2019^[16]	英国	1999—2011	多中心	队列研究	IVF/ICSI	未提及	①~④	8
Maxwell 2015^[17]	美国	2003—2012	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~②	8
Oron 2014^[18]	加拿大	2008.12—2012.12	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~⑥	8
Pereira 2016^[19]	美国	2004—2013	单中心	队列研究	IVF	day 3 vs. day 5	①③④	7
Shi 2019^[20]	中国	2006.01—2015.12	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~④	7
Spangmose 2020^[21]	丹麦、挪威、瑞典	1997—2015	多中心	队列研究	IVF/ICSI	未提及	①~⑥	9
Zhu 2014^[22]	中国	2009.01—2012.06	单中心	队列研究	IVF/ICSI	day 3 vs. day 5/6	⑤⑥	8
刘文霞2019^[23]	中国	2014.01—2016.06	单中心	队列研究	IVF/ICSI	day 3 vs. day 5	①~⑥	7

研究文献	国家	统计时间	数据来源	研究类型	受精方式	移植时间	结局指标	NOS评分
Dar 2013^[11]	加拿大	2001—2009	多中心	队列研究	IVF/ICSI	day3 vs. day5/6	①~④	9
De Vos 2015^[12]	比利时	2004.04—2009.12	单中心	队列研究	IVF/ICSI	day3 vs. day5	①~④	8
De Vos 2018^[13]	比利时	2010.09—2015.08	单中心	队列研究	IVF/ICSI	day 3 vs. day 5	①~④	8
Ishihara 2014^[14]	日本	2008—2010	多中心	队列研究	IVF/ICSI	未提及	①~⑥	8
Kalra 2012^[15]	美国	2004—2006	多中心	队列研究	IVF	day 3 vs. day5/6	①~③	8
Marconi 2019^[16]	英国	1999—2011	多中心	队列研究	IVF/ICSI	未提及	①~④	8
Maxwell 2015^[17]	美国	2003—2012	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~②	8
Oron 2014^[18]	加拿大	2008.12—2012.12	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~⑥	8
Pereira 2016^[19]	美国	2004—2013	单中心	队列研究	IVF	day 3 vs. day 5	①③④	7
Shi 2019^[20]	中国	2006.01—2015.12	单中心	队列研究	IVF/ICSI	day 2/3 vs. day 5	①~④	7
Spangmose 2020^[21]	丹麦、挪威、瑞典	1997—2015	多中心	队列研究	IVF/ICSI	未提及	①~⑥	9
Zhu 2014^[22]	中国	2009.01—2012.06	单中心	队列研究	IVF/ICSI	day 3 vs. day 5/6	⑤⑥	8
刘文霞2019^[23]	中国	2014.01—2016.06	单中心	队列研究	IVF/ICSI	day 3 vs. day 5	①~⑥	7