冻融胚胎移植妊娠结局相关影响因素分析

doi:10.12280/gjszjk.20240149

摘要/Abstract

摘要：

随着玻璃化冷冻技术的改进，冻融胚胎移植（frozen-thawed embryo transfer，FET）技术在预防卵巢过度刺激综合征、降低异位妊娠率以及提高累积妊娠率等方面发挥了重要作用。FET在辅助生殖助孕过程中周期占比逐年上升，已成为辅助生殖技术的重要组成部分。FET的妊娠结局受多种因素的影响，主要包括年龄、胚胎质量、子宫内膜厚度、子宫内膜准备方案、DNA碎片化和Y染色体微缺失等。其中年龄、胚胎质量、内膜容受性是决定FET治疗成功与否的关键因素，直接影响胚胎发育、着床和妊娠成功率。因此，识别FET妊娠结局的影响因素，并采取更精准、个体化、有针对性的预防措施以提高妊娠率已经成为研究热点。综述FET妊娠结局的相关影响因素，旨在为临床医疗决策提供科学依据。

关键词: 冻融胚胎移植, 生殖技术，辅助, 妊娠结局, 影响因素, 妊娠率

Abstract:

With the advancement of vitrification freezing technology, frozen-thawed embryo transfer (FET) plays a crucial role in assisted reproductive technology by preventing ovarian hyperstimulation syndrome, reducing ectopic pregnancy rates, and enhancing cumulative pregnancy rates. The proportion of FET cycles in assisted reproduction has been increasing annually, establishing FET as a key component of reproductive technologies. The outcome of FET pregnancies is influenced by various factors, including age, embryo quality, endometrial thickness, endometrial preparation protocols, DNA fragmentation, and Y chromosome microdeletions. Age, embryo quality, and endometrial receptivity are pivotal factors determining the success of FET treatments, directly impacting embryo development, implantation, and pregnancy success rates. Therefore, identifying the influencing factors of FET pregnancy outcome, so as to implement more precise, personalized and targeted prevention to improve pregnancy rates, has become a research hotspot. This review aims to summarize the relevant factors affecting the outcome of FET pregnancies, providing a reference for clinical decision.

Key words: Frozen-thawed embryo transfer, Reproductive techniques, assisted, Pregnancy outcome, Influencing factors, Pregnancy rate

罗莎莎, 王德婧. 冻融胚胎移植妊娠结局相关影响因素分析[J]. 国际生殖健康/计划生育杂志, 2024, 43(5): 420-424.

LUO Sha-sha, WANG De-jing. Analysis of Influencing Factors of Frozen-Thawed Embryo Transfer Pregnancy Outcome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(5): 420-424.

参考文献 49

[1]	Zhang X, Guan Q, Yu Q, et al. Estimating the effects of policies on infertility prevalence worldwide[J]. BMC Public Health, 2022, 22(1):1378. doi: 10.1186/s12889-022-13802-9. pmid: 35854262
[2]	Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo[J]. Nature, 1983, 305(5936):707-709. doi: 10.1038/305707a0.
[3]	Nagy ZP, Shapiro D, Chang CC. Vitrification of the human embryo: a more efficient and safer in vitro fertilization treatment[J]. Fertil Steril, 2020, 113(2):241-247. doi: 10.1016/j.fertnstert.2019.12.009.
[4]	Zaat T, Zagers M, Mol F, et al. Fresh versus frozen embryo transfers in assisted reproduction[J]. Cochrane Database Syst Rev, 2021, 2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.
[5]	Levi Setti PE, Cirillo F, De Cesare R, et al. Seven Years of Vitrified Blastocyst Transfers: Comparison of 3 Preparation Protocols at a Single ART Center[J]. Front Endocrinol(Lausanne), 2020, 11:346. doi: 10.3389/fendo.2020.00346.
[6]	Abdala A, Elkhatib I, Bayram A, et al. Day 5 vs day 6 single euploid blastocyst frozen embryo transfers: which variables do have an impact on the clinical pregnancy rates?[J]. J Assist Reprod Genet, 2022, 39(2):379-388. doi: 10.1007/s10815-021-02380-1.
[7]	Eleftheriadou A, Francis A, Wilcox M, et al. Frozen Blastocyst Embryo Transfer: Comparison of Protocols and Factors Influencing Outcome[J]. J Clin Med, 2022, 11(3):737. doi: 10.3390/jcm11030737.
[8]	马荣花, 简生燕, 祁淑英, 等. 影响冻融胚胎移植结局的年龄节点及相关因素分析[J]. 中国生育健康杂志, 2020, 31(5):444-448. doi: 10.3969/j.issn.1671-878X.2020.05.010.
[9]	Lin J, Huang J, Zhu Q, et al. Effect of Maternal Age on Pregnancy or Neonatal Outcomes Among 4,958 Infertile Women Using a Freeze-All Strategy[J]. Front Med(Lausanne), 2019, 6:316. doi: 10.3389/fmed.2019.00316.
[10]	宋晓霞, 袁莹莹, 胡蓉, 等. 血清AMH值与高龄冻融胚胎移植患者临床妊娠率的相关性研究[J]. 宁夏医学杂志, 2023, 45(3):236-239. doi: 10.13621/j.1001-5949.2023.03.0236.
[11]	Hu KL, Yang R, Xu H, et al. Anti-Müllerian hormone in guiding the selection of a freeze-all versus a fresh embryo transfer strategy: a cohort study[J]. J Assist Reprod Genet, 2022, 39(10):2325-2333. doi: 10.1007/s10815-022-02564-3.
[12]	Arslanca T, Ecemis T, Kiseli M, et al. Pregnancy outcome of freeze thaw cycles of polycystic ovary syndrome patients regarding the anti-Müllerian hormone percentile[J]. J Obstet Gynaecol, 2022, 42(5):1319-1324. doi: 10.1080/01443615.2021.1962819.
[13]	梁洁珩, 林冰, 何嘉欣, 等. 个体化体质量管理对冻融胚胎移植超重肥胖患者妊娠结局的影响分析[J]. 贵州医药, 2023, 47(4):668-669. doi: 10.3969/j.issn.1000-744X.2023.04.099.
[14]	Zheng Y, Dong X, Chen B, et al. Body mass index is associated with miscarriage rate and perinatal outcomes in cycles with frozen-thawed single blastocyst transfer: a retrospective cohort study[J]. BMC Pregnancy Childbirth, 2022, 22(1):118. doi: 10.1186/s12884-022-04443-2.
[15]	谢奇君, 李欣, 姜薇, 等. 女性低体质量指数对冻融胚胎移植结局的影响[J]. 国际生殖健康/计划生育杂志, 2021, 40(6):446-451. doi: 10.12280/gjszjk.20210292.
[16]	Ni Z, Mei S, You S, et al. Adverse Effects of Polycystic Ovarian Syndrome on Pregnancy Outcomes in Women With Frozen-Thawed Embryo Transfer: Propensity Score-Matched Study[J]. Front Endocrinol(Lausanne), 2022, 13:878853. doi: 10.3389/fendo.2022.878853.
[17]	Guo J, Chen Y, Jiang Y, et al. Effects of body mass index and insulin resistance on first-time assisted conception and perinatal outcomes in young polycystic ovary syndrome patients[J]. Front Endocrinol(Lausanne), 2023, 14:1170816. doi: 10.3389/fendo.2023.1170816.
[18]	Jiang X, Liu R, Liao T, et al. A Predictive Model of Live Birth Based on Obesity and Metabolic Parameters in Patients With PCOS Undergoing Frozen-Thawed Embryo Transfer[J]. Front Endocrinol(Lausanne), 2021, 12:799871. doi: 10.3389/fendo.2021.799871.
[19]	Zhang Y, Wu W, Liu Y, et al. The impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer[J]. BMC Pregnancy Childbirth, 2020, 20(1):677. doi: 10.1186/s12884-020-03383-z.
[20]	Zhang CH, Chen C, Wang JR, et al. An endometrial receptivity scoring system basing on the endometrial thickness, volume, echo, peristalsis, and blood flow evaluated by ultrasonography[J]. Front Endocrinol(Lausanne), 2022, 13:907874. doi: 10.3389/fendo.2022.907874.
[21]	Değer U, Kalı Z, Çağıran F. Endometrial thickness is a good predictor of clinical pregnancy and live birth rates in fresh and frozen-thawed embryo transfer cycles[J]. Eur Rev Med Pharmacol Sci, 2023, 27(13):6351-6358. doi: 10.26355/eurrev_202307_32995.
[22]	朱素芹, 姜雯雯, 李榕珊, 等. 冻融胚胎移植周期子宫内膜厚度对不孕症女性临床结局的影响[J]. 福建医药杂志, 2022, 44(6):51-54. doi: 10.3969/j.issn.1002-2600.2022.06.014.
[23]	Zhang M, Li J, Fu X, et al. Endometrial thickness is an independent risk factor of hypertensive disorders of pregnancy: a retrospective study of 13,458 patients in frozen-thawed embryo transfers[J]. Reprod Biol Endocrinol, 2022, 20(1):93. doi: 10.1186/s12958-022-00965-8.
[24]	Zhang Q, Wang X, Zhang Y, et al. Nomogram prediction for the prediction of clinical pregnancy in Freeze-thawed Embryo Transfer[J]. BMC Pregnancy Childbirth, 2022, 22(1):629. doi: 10.1186/s12884-022-04958-8.
[25]	Mayer RB, Ebner T, Weiss C, et al. The Role of Endometrial Volume and Endometrial and Subendometrial Vascularization Parameters in a Frozen Embryo Transfer Cycle[J]. Reprod Sci, 2019, 26(7):1013-1018. doi: 10.1177/1933719118804421. pmid: 30419800
[26]	Haas J, Smith R, Zilberberg E, et al. Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers[J]. Fertil Steril, 2019, 112(3):503-509.e1. doi: 10.1016/j.fertnstert.2019.05.001. pmid: 31248618
[27]	Yaprak E, Şükür YE, Özmen B, et al. Endometrial compaction is associated with the increased live birth rate in artificial frozen-thawed embryo transfer cycles[J]. Hum Fertil(Camb), 2023, 26(3):550-556. doi: 10.1080/14647273.2021.1966703.
[28]	Ju W, Wei C, Lu X, et al. Endometrial compaction is associated with the outcome of artificial frozen-thawed embryo transfer cycles: a retrospective cohort study[J]. J Assist Reprod Genet, 2023, 40(7):1649-1660. doi: 10.1007/s10815-023-02809-9.
[29]	彭默然, 梁雪琪, 谭丽. 不同内膜准备方案对FET助孕结局的影响[J]. 生殖医学杂志, 2023, 32(12):1826-1831. doi: 10.3969/j.issn.1004-3845.2023.12.010.
[30]	Lou L, Xu Y, Lv M, et al. Comparison of different endometrial preparation protocols on frozen embryo transfer pregnancy outcome in patients with normal ovulation[J]. Reprod Biomed Online, 2022, 45(6):1182-1187. doi: 10.1016/j.rbmo.2022.06.026.
[31]	Guan L, Wu H, Wei C, et al. The effect of mildly stimulated cycle versus artificial cycle on pregnancy outcomes in overweight/obese women with PCOS prior to frozen embryo transfer: a retrospective cohort study[J]. BMC Pregnancy Childbirth, 2022, 22(1):394. doi: 10.1186/s12884-022-04728-6.
[32]	Zeng C, Lu RH, Li X, et al. Effect of frozen-thawed embryo transfer with a poor-quality embryo and a good-quality embryo on pregnancy and neonatal outcomes[J]. Reprod Biol Endocrinol, 2024, 22(1):26. doi: 10.1186/s12958-024-01194-x.
[33]	杜威, 王娟, 田可可, 等. 玻璃化冷冻胚胎解冻后卵裂球损伤与增殖对移植影响[J]. 社区医学杂志, 2020, 18(7):494-496. doi: 10.19790/j.cnki.JCM.2020.07.07
[34]	Liao Q, Zhang Q, Feng X, et al. Development of deep learning algorithms for predicting blastocyst formation and quality by time-lapse monitoring[J]. Commun Biol, 2021, 4(1):415. doi: 10.1038/s42003-021-01937-1. pmid: 33772211
[35]	Ueno S, Berntsen J, Ito M, et al. O-006 Annotation-free embryo score calculated by iDAScore^® correlated with live birth and has no correlation with neonatal outcomes after single vitrified-warmed blastocyst transfer[J]. Hum Reprod, 2022, 37(Suppl 1):deac104.006. doi:10.1093/humrep/deac104.006.
[36]	耿旭景, 毛跟红, 赵冬梅, 等. 移植胚胎数对冻融胚胎复苏移植周期临床结局的影响[J]. 中国妇产科临床杂志, 2020, 21(3):310-311. doi: 10.13390/j.issn.1672-1861.2020.03.034.
[37]	Ma S, Peng Y, Hu L, et al. Comparisons of benefits and risks of single embryo transfer versus double embryo transfer: a systematic review and meta-analysis[J]. Reprod Biol Endocrinol, 2022, 20(1):20. doi: 10.1186/s12958-022-00899-1.
[38]	Namath A, Jahandideh S, Devine K, et al. Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and preimplantation genetic testing: a retrospective analysis[J]. Fertil Steril, 2021, 115(6):1471-1477. doi: 10.1016/j.fertnstert.2021.01.010. pmid: 33691932
[39]	Holden EC, Kashani BN, Morelli SS, et al. Improved outcomes after blastocyst-stage frozen-thawed embryo transfers compared with cleavage stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study[J]. Fertil Steril, 2018, 110(1):89-94.e2. doi: 10.1016/j.fertnstert.2018.03.033. pmid: 29908769
[40]	余柯达, 毛佳婷, 包云, 等. 冻融卵裂期胚胎与囊胚移植的妊娠结局及第二性别比的比较[J]. 浙江医学, 2023, 45(12):1274-1278. doi: 10.12056/j.issn.1006-2785.2023.45.12.2022-2885.
[41]	Lim YH, Sim PK, Nadkarni P. A retrospective comparative study of double cleavage-stage embryo transfer versus single blastocyst in frozen-thawed cycles[J]. Middle East Fertility Soc J, 2024, 29(1):17. doi: 10.1186/s43043-024-00177-7.
[42]	Li X, Guo P, Blockeel C, et al. Storage duration of vitrified embryos does not affect pregnancy and neonatal outcomes after frozen-thawed embryo transfer[J]. Front Endocrinol(Lausanne), 2023, 14:1148411. doi: 10.3389/fendo.2023.1148411.
[43]	芦亚琼, 何钰辉, 王芳, 等. 冻融长期冷冻保存胚胎对妊娠结局的影响[J]. 中国妇幼健康研究, 2020, 31(10):1333-1336. doi: 10.3969/j.issn.1673-5293.2020.10.008.
[44]	Zhang F, Li J, Liang Z, et al. Sperm DNA fragmentation and male fertility: a retrospective study of 5114 men attending a reproductive center[J]. J Assist Reprod Genet, 2021, 38(5):1133-1141. doi: 10.1007/s10815-021-02120-5.
[45]	Wang QX, Wang X, Yu MY, et al. Random sperm DNA fragmentation index is not associated with clinical outcomes in day-3 frozen embryo transfer[J]. Asian J Androl, 2022, 24(1):109-115. doi: 10.4103/aja.aja_17_21.
[46]	李焕, 邓浩, 赵军, 等. 精子DNA碎片率在体外受精-胚胎移植中对冻融囊胚移植结局的影响[J]. 中华男科学杂志, 2020, 26(5):422-426. doi: 10.13263/j.cnki.nja.2020.05.006.
[47]	杨舒婷, 周明连, 汤欣欣, 等. 不育男性患者Y染色体AZF区域微缺失及临床表现[J]. 中国计划生育学杂志, 2020, 28(9):1435-1438. doi: 10.3969/j.issn.1004-8189.2020.09.025.
[48]	Gambera L, Governini L, De Leo V, et al. Successful multiple pregnancy achieved after transfer of frozen embryos obtained via intracytoplasmic sperm injection with testicular sperm from an AZFc-deleted man[J]. Fertil Steril, 2010, 94(6):2330.e1-e3. doi: 10.1016/j.fertnstert.2010.03.069.
[49]	Colaco S, Modi D. Azoospermia factor c microdeletions and outcomes of assisted reproductive technology: a systematic review and meta-analysis[J]. Fertil Steril, 2024, 121(1):63-71. doi: 10.1016/j.fertnstert.2023.10.029.